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Cellular and Molecular Life Sciences

, Volume 72, Issue 2, pp 285–306 | Cite as

The mammalian Hippo pathway: regulation and function of YAP1 and TAZ

Review

Abstract

The Hippo pathway was originally identified as the signaling that controls organ size in Drosophila, with the core architecture conserved in mammals. In the mammalian Hippo pathway, mammalian Ste20-like kinases (MST1/2) and large tumor suppressor kinases (LATS1/2) regulate transcriptional co-activators, Yes-associated protein (YAP1) and Transcriptional co-activator with a PDZ-binding motif (TAZ). The Hippo pathway was initially thought to be quite straightforward; however, the identification of additional components has revealed its inherent complexity. Regulation of YAP1 and TAZ is not always dependent on MST1/2 and LATS1/2. MST1/2 and LATS1/2 play various YAP1/TAZ-independent roles, while YAP1 and TAZ cross-talk with other signaling pathways. In this review we focus on YAP1 and TAZ and discuss their regulation, function, and the consequences of their dysregulation.

Keywords

Cancer Stem cell Cell differentiation Development Regeneration Tumor suppressor 

References

  1. 1.
    Justice RW, Zilian O, Woods DF, Noll M, Bryant PJ (1995) The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dystrophy kinase and is required for the control of cell shape and proliferation. Genes Dev 9:534–546PubMedGoogle Scholar
  2. 2.
    Xu T, Wang W, Zhang S, Stewart RA, Yu W (1995) Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development 121:1053–1063PubMedGoogle Scholar
  3. 3.
    Harvey KF, Pfleger CM, Hariharan IK (2003) The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis. Cell 114:457–467PubMedGoogle Scholar
  4. 4.
    Pantalacci S, Tapon N, Léopold P (2003) The Salvador partner Hippo promotes apoptosis and cell-cycle exit in Drosophila. Nat Cell Biol 5:921–927PubMedGoogle Scholar
  5. 5.
    Udan RS, Kango-Singh M, Nolo R, Tao C, Halder G (2003) Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway. Nat Cell Biol 5:914–920PubMedGoogle Scholar
  6. 6.
    Wu S, Huang J, Dong J, Pan D (2003) hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts. Cell 114:445–456PubMedGoogle Scholar
  7. 7.
    Jia J, Zhang W, Wang B, Trinko R, Jiang J (2003) The Drosophila Ste20 family kinase dMST functions as a tumor suppressor by restricting cell proliferation and promoting apoptosis. Genes Dev 17:2514–2519PubMedCentralPubMedGoogle Scholar
  8. 8.
    Tapon N, Harvey KF, Bell DW, Wahrer DC, Schiripo TA, Haber D, Hariharan IK (2002) Salvador promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines. Cell 110:467–478PubMedGoogle Scholar
  9. 9.
    Lai ZC, Wei X, Shimizu T, Ramos E, Rohrbaugh M, Nikolaidis N, Ho LL, Li Y (2005) Control of cell proliferation and apoptosis by mob as tumor suppressor, mats. Cell 120:675–685PubMedGoogle Scholar
  10. 10.
    Huang J, Wu S, Barrera J, Matthews K, Pan D (2005) The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP. Cell 122:421–434PubMedGoogle Scholar
  11. 11.
    St John MA, Tao W, Fei X, Fukumoto R, Carcangiu ML, Brownstein DG, Parlow AF, McGrath J, Xu T (1999) Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction. Nat Genet 21:182–186PubMedGoogle Scholar
  12. 12.
    Hamaratoglu F, Willecke M, Kango-Singh M, Nolo R, Hyun E, Tao C, Jafar-Nejad H, Halder G (2006) The tumour-suppressor genes NF2/Merlin and expanded act through Hippo signalling to regulate cell proliferation and apoptosis. Nat Cell Biol 8:27–36PubMedGoogle Scholar
  13. 13.
    Sudol M (1994) Yes-associated protein (YAP65) is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes proto-oncogene product. Oncogene 9:2145–2152PubMedGoogle Scholar
  14. 14.
    Kanai F, Marignani PA, Sarbassova D, Yagi R, Hall RA, Donowitz M, Hisaminato A, Fujiwara T, Ito Y, Cantley LC, Yaffe MB (2000) TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins. EMBO J 19:6778–6791PubMedCentralPubMedGoogle Scholar
  15. 15.
    Qin F, Tian J, Zhou D, Chen L (2013) Mst1 and Mst2 kinases: regulations and diseases. Cell Biosci 3:31PubMedCentralPubMedGoogle Scholar
  16. 16.
    Hergovich A (2013) Regulation and functions of mammalian LATS/NDR kinases: looking beyond canonical Hippo signalling. Cell Biosci 3:32PubMedCentralPubMedGoogle Scholar
  17. 17.
    Gaffney CJ, Oka T, Mazack V, Hilman D, Gat U, Muramatsu T, Inazawa J, Golden A, Carey DJ, Farooq A, Tromp G, Sudol M (2012) Identification, basic characterization and evolutionary analysis of differentially spliced mRNA isoforms of human YAP1 gene. Gene 509:215–222PubMedCentralPubMedGoogle Scholar
  18. 18.
    Webb C, Upadhyay A, Giuntini F, Eggleston I, Furutani-Seiki M, Ishima R, Bagby S (2011) Structural features and ligand binding properties of tandem WW domains from YAP and TAZ, nuclear effectors of the Hippo pathway. Biochemistry 50:3300–3309PubMedGoogle Scholar
  19. 19.
    Howell M, Borchers C, Milgram SL (2004) Heterogeneous nuclear ribonuclear protein U associates with YAP and regulates its co-activation of Bax transcription. J Biol Chem 279:26300–26306PubMedGoogle Scholar
  20. 20.
    Lei QY, Zhang H, Zhao B, Zha ZY, Bai F, Pei XH, Zhao S, Xiong Y, Guan KL (2008) TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway. Mol Cell Biol 28:2426–2436PubMedCentralPubMedGoogle Scholar
  21. 21.
    Basu S, Totty NF, Irwin MS, Sudol M, Downward J (2003) Akt phosphorylates the yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis. Mol Cell 11:11–23PubMedGoogle Scholar
  22. 22.
    Liu CY, Zha ZY, Zhou X, Zhang H, Huang W, Zhao D, Li T, Chan SW, Lim CJ, Hong W, Zhao S, Xiong Y, Lei QY, Guan KL (2010) The hippo tumor pathway promotes TAZ degradation by phosphorylating a phosphodegron and recruiting the SCF{beta}-TrCP E3 ligase. J Biol Chem 285:37159–37169PubMedCentralPubMedGoogle Scholar
  23. 23.
    Zhao B, Li L, Tumaneng K, Wang CY, Guan KL (2010) A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP). Genes Dev 24:72–85PubMedCentralPubMedGoogle Scholar
  24. 24.
    Huang W, Lv X, Liu C, Zha Z, Zhang H, Jiang Y, Xiong Y, Lei QY, Guan KL (2012) The N-terminal phosphodegron targets TAZ/WWTR1 protein for SCFβ-TrCP-dependent degradation in response to phosphatidylinositol 3-kinase inhibition. J Biol Chem 287:26245–26253PubMedCentralPubMedGoogle Scholar
  25. 25.
    Tamm C, Böwer N, Annerén C (2011) Regulation of mouse embryonic stem cell self-renewal by a Yes-YAP-TEAD2 signaling pathway downstream of LIF. J Cell Sci 124:1136–1144PubMedGoogle Scholar
  26. 26.
    Rosenbluh J, Nijhawan D, Cox AG, Li X, Neal JT, Schafer EJ, Zack TI, Wang X, Tsherniak A, Schinzel AC, Shao DD, Schumacher SE, Weir BA, Vazquez F, Cowley GS, Root DE, Mesirov JP, Beroukhim R, Kuo CJ, Goessling W, Hahn WC (2012) β-Catenin-driven cancers require a YAP1 transcriptional complex for survival and tumorigenesis. Cell 151:1457–1473PubMedCentralPubMedGoogle Scholar
  27. 27.
    Zaidi SK, Sullivan AJ, Medina R, Ito Y, van Wijnen AJ, Stein JL, Lian JB, Stein GS (2004) Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress transcription. EMBO J 23:790–799PubMedCentralPubMedGoogle Scholar
  28. 28.
    Levy D, Adamovich Y, Reuven N, Shaul Y (2008) Yap1 phosphorylation by c-Abl is a critical step in selective activation of proapoptotic genes in response to DNA damage. Mol Cell 29:350–361PubMedGoogle Scholar
  29. 29.
    Levy D, Adamovich Y, Reuven N, Shaul Y (2007) The Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73. Cell Death Differ 14:743–751PubMedGoogle Scholar
  30. 30.
    Levy D, Reuven N, Shaul Y (2008) A regulatory circuit controlling Itch-mediated p73 degradation by Runx. J Biol Chem 283:27462–27468PubMedGoogle Scholar
  31. 31.
    Strano S, Munarriz E, Rossi M, Castagnoli L, Shaul Y, Sacchi A, Oren M, Sudol M, Cesareni G, Blandino G (2001) Physical interaction with Yes-associated protein enhances p73 transcriptional activity. J Biol Chem 276:15164–15173PubMedGoogle Scholar
  32. 32.
    Danovi SA, Rossi M, Gudmundsdottir K, Yuan M, Melino G, Basu S (2008) Yes-associated protein (YAP) is a critical mediator of c-Jun-dependent apoptosis. Cell Death Differ 15:217–219PubMedGoogle Scholar
  33. 33.
    Tomlinson V, Gudmundsdottir K, Luong P, Leung KY, Knebel A, Basu S (2010) JNK phosphorylates yes-associated protein (YAP) to regulate apoptosis. Cell Death Dis 1:e29PubMedCentralPubMedGoogle Scholar
  34. 34.
    Yang S, Zhang L, Liu M, Chong R, Ding SJ, Chen Y, Dong J (2013) CDK1 phosphorylation of YAP promotes mitotic defects and cell motility and is essential for neoplastic transformation. Cancer Res 73:6722–6733PubMedGoogle Scholar
  35. 35.
    Yim H, Sung CK, You J, Tian Y, Benjamin T (2011) Nek1 and TAZ interact to maintain normal levels of polycystin 2. J Am Soc Nephrol 22:832–837PubMedCentralPubMedGoogle Scholar
  36. 36.
    Fausti F, Di Agostino S, Cioce M, Bielli P, Sette C, Pandolfi PP, Oren M, Sudol M, Strano S, Blandino G (2013) ATM kinase enables the functional axis of YAP, PML and p53 to ameliorate loss of Werner protein-mediated oncogenic senescence. Cell Death Differ 20:1498–1509PubMedCentralPubMedGoogle Scholar
  37. 37.
    Liu CY, Lv X, Li T, Xu Y, Zhou X, Zhao S, Xiong Y, Lei QY, Guan KL (2011) PP1 cooperates with ASPP2 to dephosphorylate and activate TAZ. J Biol Chem 286:5558–5566PubMedCentralPubMedGoogle Scholar
  38. 38.
    Cai H, Xu Y (2013) The role of LPA and YAP signaling in long-term migration of human ovarian cancer cells. Cell Commun Signal 11:31PubMedCentralPubMedGoogle Scholar
  39. 39.
    Schlegelmilch K, Mohseni M, Kirak O, Pruszak J, Rodriguez JR, Zhou D, Kreger BT, Vasioukhin V, Avruch J, Brummelkamp TR, Camargo FD (2011) Yap1 acts downstream of α-catenin to control epidermal proliferation. Cell 144:782–795PubMedCentralPubMedGoogle Scholar
  40. 40.
    Huang JM, Nagatomo I, Suzuki E, Mizuno T, Kumagai T, Berezov A, Zhang H, Karlan B, Greene MI, Wang Q (2013) YAP modifies cancer cell sensitivity to EGFR and survivin inhibitors and is negatively regulated by the non-receptor type protein tyrosine phosphatase 14. Oncogene 32:2220–2229PubMedCentralPubMedGoogle Scholar
  41. 41.
    Liu X, Yang N, Figel SA, Wilson KE, Morrison CD, Gelman IH, Zhang J (2013) PTPN14 interacts with and negatively regulates the oncogenic function of YAP. Oncogene 32:1266–1273PubMedGoogle Scholar
  42. 42.
    Wang W, Huang J, Wang X, Yuan J, Li X, Feng L, Park JI, Chen J (2012) PTPN14 is required for the density-dependent control of YAP1. Genes Dev 26:1959–1971PubMedCentralPubMedGoogle Scholar
  43. 43.
    Hata S, Hirayama J, Kajiho H, Nakagawa K, Hata Y, Katada T, Furutani-Seiki M, Nishina H (2012) A novel acetylation cycle of transcription co-activator Yes-associated protein that is downstream of Hippo pathway is triggered in response to SN2 alkylating agents. J Biol Chem 287:22089–22098PubMedCentralPubMedGoogle Scholar
  44. 44.
    Oudhoff MJ, Freeman SA, Couzens AL, Antignano F, Kuznetsova E, Min PH, Northrop JP, Lehnertz B, Barsyte-Lovejoy D, Vedadi M, Arrowsmith CH, Nishina H, Gold MR, Rossi FM, Gingras AC, Zaph C (2013) Control of the hippo pathway by Set7-dependent methylation of Yap. Dev Cell 26:188–194PubMedGoogle Scholar
  45. 45.
    Lapi E, Di Agostino S, Donzelli S, Gal H, Domany E, Rechavi G, Pandolfi PP, Givol D, Strano S, Lu X, Blandino G (2008) PML, YAP, and p73 are components of a proapoptotic autoregulatory feedback loop. Mol Cell 32:803–814PubMedGoogle Scholar
  46. 46.
    Cappello S, Gray MJ, Badouel C, Lange S, Einsiedler M, Srour M, Chitayat D, Hamdan FF, Jenkins ZA, Morgan T, Preitner N, Uster T, Thomas J, Shannon P, Morrison V, Di Donato N, Van Maldergem L, Neuhann T, Newbury-Ecob R, Swinkells M, Terhal P, Wilson LC, Zwijnenburg PJ, Sutherland-Smith AJ, Black MA, Markie D, Michaud JL, Simpson MA, Mansour S, McNeill H, Götz M, Robertson SP (2013) Mutations in genes encoding the cadherin receptor-ligand pair DCHS1 and FAT4 disrupt cerebral cortical development. Nat Genet 45:1300–1308PubMedGoogle Scholar
  47. 47.
    Murphy AJ, Pierce J, de Caestecker C, Libes J, Neblett D, de Caestecker M, Perantoni AO, Tanigawa S, Anderson JR, Dome JS, Das A, Carroll TJ, Lovvorn HN (2014) Aberrant activation, nuclear localization, and phosphorylation of Yes-associated protein-1 in the embryonic kidney and Wilms tumor. Pediatr Blood Cancer 61:198–205PubMedCentralPubMedGoogle Scholar
  48. 48.
    Saburi S, Hester I, Fischer E, Pontoglio M, Eremina V, Gessler M, Quaggin SE, Harrison R, Mount R, McNeill H (2008) Loss of Fat4 disrupts PCP signaling and oriented cell division and leads to cystic kidney disease. Nat Genet 40:1010–1015PubMedGoogle Scholar
  49. 49.
    Makita R, Uchijima Y, Nishiyama K, Amano T, Chen Q, Takeuchi T, Mitani A, Nagase T, Yatomi Y, Aburatani H, Nakagawa O, Small EV, Cobo-Stark P, Igarashi P, Murakami M, Tominaga J, Sato T, Asano T, Kurihara Y, Kurihara H (2008) Multiple renal cysts, urinary concentration defects, and pulmonary emphysematous changes in mice lacking TAZ. Am J Physiol Renal Physiol 294:F542–F553PubMedGoogle Scholar
  50. 50.
    Hossain Z, Ali SM, Ko HL, Xu J, Ng CP, Guo K, Qi Z, Ponniah S, Hong W, Hunziker W (2007) Glomerulocystic kidney disease in mice with a targeted inactivation of Wwtr1. Proc Natl Acad Sci USA 104:1631–1636PubMedCentralPubMedGoogle Scholar
  51. 51.
    Xu Y, Stamenkovic I, Yu Q (2010) CD44 attenuates activation of the hippo signaling pathway and is a prime therapeutic target for glioblastoma. Cancer Res 70:2455–2464PubMedCentralPubMedGoogle Scholar
  52. 52.
    Tsuneki M, Madri JA (2014) CD44 regulation of endothelial cell proliferation and apoptosis via modulation of CD31 and VE-cadherin expression. J Biol Chem 289:5357–5370PubMedGoogle Scholar
  53. 53.
    Bao Y, Nakagawa K, Yang Z, Ikeda M, Withanage K, Ishigami-Yuasa M, Okuno Y, Hata S, Nishina H, Hata Y (2011) A cell-based assay to screen stimulators of the Hippo pathway reveals the inhibitory effect of dobutamine on the YAP-dependent gene transcription. J Biochem 150:199–208PubMedGoogle Scholar
  54. 54.
    Mo JS, Yu FX, Gong R, Brown JH, Guan KL (2012) Regulation of the Hippo-YAP pathway by protease-activated receptors (PARs). Genes Dev 26:2138–2143PubMedCentralPubMedGoogle Scholar
  55. 55.
    Yu FX, Zhao B, Panupinthu N, Jewell JL, Lian I, Wang LH, Zhao J, Yuan H, Tumaneng K, Li H, Fu XD, Mills GB, Guan KL (2012) Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell 150:780–791PubMedCentralPubMedGoogle Scholar
  56. 56.
    Miller E, Yang J, DeRan M, Wu C, Su AI, Bonamy GM, Liu J, Peters EC, Wu X (2012) Identification of serum-derived sphingosine-1-phosphate as a small molecule regulator of YAP. Chem Biol 19:955–962PubMedGoogle Scholar
  57. 57.
    Yu FX, Zhang Y, Park HW, Jewell JL, Chen Q, Deng Y, Pan D, Taylor SS, Lai ZC, Guan KL (2013) Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation. Genes Dev 27:1223–1232PubMedCentralPubMedGoogle Scholar
  58. 58.
    Kim M, Lee S, Kuninaka S, Saya H, Lee H, Lim DS (2013) cAMP/PKA signalling reinforces the LATS-YAP pathway to fully suppress YAP in response to actin cytoskeletal changes. EMBO J 32:1543–1555PubMedCentralPubMedGoogle Scholar
  59. 59.
    Yu FX, Luo J, Mo JS, Liu G, Kim YC, Meng Z, Zhao L, Peyman G, Ouyang H, Jiang W, Zhao J, Chen X, Zhang L, Wang CY, Bastian BC, Zhang K, Guan KL (2014) Mutant Gq/11 promote uveal melanoma tumorigenesis by activating YAP. Cancer Cell 25:822–830PubMedGoogle Scholar
  60. 60.
    Feng X, Degese MS, Iglesias-Bartolome R, Vaque JP, Molinolo AA, Rodrigues M, Zaidi MR, Ksander BR, Merlino G, Sodhi A, Chen Q, Gutkind JS (2014) Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry. Cancer Cell 25:831–845PubMedGoogle Scholar
  61. 61.
    Chen D, Sun Y, Wei Y, Zhang P, Rezaeian AH, Teruya-Feldstein J, Gupta S, Liang H, Lin HK, Hung MC, Ma L (2012) LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker. Nat Med 18:1511–1517PubMedCentralPubMedGoogle Scholar
  62. 62.
    Cooper J, Giancotti FG (2014) Molecular insights into NF2/Merlin tumor suppressor function. FEBS Lett 588(16):2743–2752Google Scholar
  63. 63.
    Zhang N, Bai H, David KK, Dong J, Zheng Y, Cai J, Giovannini M, Liu P, Anders RA, Pan D (2010) The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev Cell 19:27–38PubMedCentralPubMedGoogle Scholar
  64. 64.
    Gladden AB, Hebert AM, Schneeberger EE, McClatchey AI (2010) The NF2 tumor suppressor, Merlin, regulates epidermal development through the establishment of a junctional polarity complex. Dev Cell 19:727–739PubMedCentralPubMedGoogle Scholar
  65. 65.
    Angus L, Moleirinho S, Herron L, Sinha A, Zhang X, Niestrata M, Dholakia K, Prystowsky MB, Harvey KF, Reynolds PA, Gunn-Moore FJ (2012) Willin/FRMD6 expression activates the Hippo signaling pathway kinases in mammals and antagonizes oncogenic YAP. Oncogene 31:238–250PubMedGoogle Scholar
  66. 66.
    Genevet A, Wehr MC, Brain R, Thompson BJ, Tapon N (2010) Kibra is a regulator of the Salvador/Warts/Hippo signaling network. Dev Cell 18:300–308PubMedCentralPubMedGoogle Scholar
  67. 67.
    Yu J, Zheng Y, Dong J, Klusza S, Deng WM, Pan D (2010) Kibra functions as a tumor suppressor protein that regulates Hippo signaling in conjunction with Merlin and expanded. Dev Cell 18:288–299PubMedCentralPubMedGoogle Scholar
  68. 68.
    Xiao L, Chen Y, Ji M, Dong J (2011) KIBRA regulates Hippo signaling activity via interactions with large tumor suppressor kinases. J Biol Chem 286:7788–7796PubMedCentralPubMedGoogle Scholar
  69. 69.
    Moleirinho S, Guerrant W, Kissil JL (2014) The Angiomotins: from discovery to function. FEBS Lett 588(16):2693–2703Google Scholar
  70. 70.
    Wells CD, Fawcett JP, Traweger A, Yamanaka Y, Goudreault M, Elder K, Kulkarni S, Gish G, Virag C, Lim C, Colwill K, Starostine A, Metalnikov P, Pawson T (2006) A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells. Cell 125:535–548PubMedGoogle Scholar
  71. 71.
    Yi C, Troutman S, Fera D, Stemmer-Rachamimov A, Avila JL, Christian N, Persson NL, Shimono A, Speicher DW, Marmorstein R, Holmgren L, Kissil JL (2011) A tight junction-associated Merlin-angiomotin complex mediates Merlin’s regulation of mitogenic signaling and tumor suppressive functions. Cancer Cell 19:527–540PubMedCentralPubMedGoogle Scholar
  72. 72.
    Zhao B, Li L, Lu Q, Wang LH, Liu CY, Lei Q, Guan KL (2011) Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein. Genes Dev 25:51–63PubMedCentralPubMedGoogle Scholar
  73. 73.
    Chan SW, Lim CJ, Chong YF, Pobbati AV, Huang C, Hong W (2011) Hippo pathway-independent restriction of TAZ and YAP by angiomotin. J Biol Chem 286:7018–7026PubMedCentralPubMedGoogle Scholar
  74. 74.
    Yi C, Shen Z, Stemmer-Rachamimov A, Dawany N, Troutman S, Showe LC, Liu Q, Shimono A, Sudol M, Holmgren L, Stanger BZ, Kissil JL (2013) The p130 isoform of angiomotin is required for Yap-mediated hepatic epithelial cell proliferation and tumorigenesis. Sci Signal 6:ra77PubMedCentralPubMedGoogle Scholar
  75. 75.
    Das Thakur M, Feng Y, Jagannathan R, Seppa MJ, Skeath JB, Longmore GD (2010) Ajuba LIM proteins are negative regulators of the Hippo signaling pathway. Curr Biol 20:657–662PubMedGoogle Scholar
  76. 76.
    Reddy BV, Irvine KD (2013) Regulation of Hippo signaling by EGFR-MAPK signaling through Ajuba family proteins. Dev Cell 24:459–471PubMedCentralPubMedGoogle Scholar
  77. 77.
    Sun G, Irvine KD (2013) Ajuba family proteins link JNK to Hippo signaling. Sci Signal 6:ra81PubMedGoogle Scholar
  78. 78.
    Codelia VA, Sun G, Irvine KD (2014) Regulation of YAP by mechanical strain through jnk and hippo signaling. Curr Biol 24(17):2012–2017Google Scholar
  79. 79.
    Tanaka I, Osada H, Fujii M, Fukatsu A, Hida T, Horio Y, Kondo Y, Sato A, Hasegawa Y, Tsujimura T, Sekido Y (2013) LIM-domain protein AJUBA suppresses malignant mesothelioma cell proliferation via Hippo signaling cascade. Oncogene. doi: 10.1038/onc.2013.528
  80. 80.
    Oka T, Remue E, Meerschaert K, Vanloo B, Boucherie C, Gfeller D, Bader GD, Sidhu SS, Vandekerckhove J, Gettemans J, Sudol M (2010) Functional complexes between YAP2 and ZO-2 are PDZ domain-dependent, and regulate YAP2 nuclear localization and signalling. Biochem J 432:461–472PubMedGoogle Scholar
  81. 81.
    Remue E, Meerschaert K, Oka T, Boucherie C, Vandekerckhove J, Sudol M, Gettemans J (2010) TAZ interacts with zonula occludens-1 and -2 proteins in a PDZ-1 dependent manner. FEBS Lett 584:4175–4180PubMedGoogle Scholar
  82. 82.
    Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M, Zanconato F, Le Digabel J, Forcato M, Bicciato S, Elvassore N, Piccolo S (2011) Role of YAP/TAZ in mechanotransduction. Nature 474:179–183PubMedGoogle Scholar
  83. 83.
    Sorrentino G, Ruggeri N, Specchia V, Cordenonsi M, Mano M, Dupont S, Manfrin A, Ingallina E, Sommaggio R, Piazza S, Rosato A, Piccolo S, Del Sal G (2014) Metabolic control of YAP and TAZ by the mevalonate pathway. Nat Cell Biol 16:357–366PubMedGoogle Scholar
  84. 84.
    Reginensi A, Scott RP, Gregorieff A, Bagherie-Lachidan M, Chung C, Lim DS, Pawson T, Wrana J, McNeill H (2013) Yap- and Cdc42-dependent nephrogenesis and morphogenesis during mouse kidney development. PLoS Genet 9:e1003380PubMedCentralPubMedGoogle Scholar
  85. 85.
    Fernández BG, Gaspar P, Brás-Pereira C, Jezowska B, Rebelo SR, Janody F (2011) Actin-Capping Protein and the Hippo pathway regulate F-actin and tissue growth in Drosophila. Development 138:2337–2346PubMedGoogle Scholar
  86. 86.
    Calvo F, Ege N, Grande-Garcia A, Hooper S, Jenkins RP, Chaudhry SI, Harrington K, Williamson P, Moeendarbary E, Charras G, Sahai E (2013) Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat Cell Biol 15:637–646PubMedGoogle Scholar
  87. 87.
    Pelissier FA, Garbe JC, Ananthanarayanan B, Miyano M, Lin C, Jokela T, Kumar S, Stampfer MR, Lorens JB, LaBarge MA (2014) Age-related dysfunction in mechanotransduction impairs differentiation of human mammary epithelial progenitors. Cell Rep 7:1926–1939PubMedGoogle Scholar
  88. 88.
    Sun Y, Yong KM, Villa-Diaz LG, Zhang X, Chen W, Philson R, Weng S, Xu H, Krebsbach PH, Fu J (2014) Hippo/YAP-mediated rigidity-dependent motor neuron differentiation of human pluripotent stem cells. Nat Mater 13:599–604PubMedCentralPubMedGoogle Scholar
  89. 89.
    Boggiano JC, Vanderzalm PJ, Fehon RG (2011) Tao-1 phosphorylates Hippo/MST kinases to regulate the Hippo-Salvador-Warts tumor suppressor pathway. Dev Cell 21:888–895PubMedCentralPubMedGoogle Scholar
  90. 90.
    Poon CL, Lin JI, Zhang X, Harvey KF (2011) The sterile 20-like kinase Tao-1 controls tissue growth by regulating the Salvador-Warts-Hippo pathway. Dev Cell 21:896–906PubMedGoogle Scholar
  91. 91.
    Wehr MC, Holder MV, Gailite I, Saunders RE, Maile TM, Ciirdaeva E, Instrell R, Jiang M, Howell M, Rossner MJ, Tapon N (2013) Salt-inducible kinases regulate growth through the Hippo signalling pathway in Drosophila. Nat Cell Biol 15:61–71PubMedCentralPubMedGoogle Scholar
  92. 92.
    Mohseni M, Sun J, Lau A, Curtis S, Goldsmith J, Fox VL, Wei C, Frazier M, Samson O, Wong KK, Kim C, Camargo FD (2014) A genetic screen identifies an LKB1-MARK signalling axis controlling the Hippo-YAP pathway. Nat Cell Biol 16:108–117PubMedCentralPubMedGoogle Scholar
  93. 93.
    Gao Y, Zhang W, Han X, Li F, Wang X, Wang R, Fang Z, Tong X, Yao S, Feng Y, Sun Y, Hou Y, Yang Z, Guan K, Chen H, Zhang L, Ji H (2014) YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma through ZEB2-dependent DNp63 repression. Nat Commun 5:4629PubMedGoogle Scholar
  94. 94.
    Serrano I, McDonald PC, Lock F, Muller WJ, Dedhar S (2013) Inactivation of the Hippo tumour suppressor pathway by integrin-linked kinase. Nat Commun 4:2976PubMedCentralPubMedGoogle Scholar
  95. 95.
    Poon CL, Zhang X, Lin JI, Manning SA, Harvey KF (2012) Homeodomain-interacting protein kinase regulates Hippo pathway-dependent tissue growth. Curr Biol 22:1587–1594PubMedGoogle Scholar
  96. 96.
    Polesello C, Huelsmann S, Brown NH, Tapon N (2006) The Drosophila RASSF homolog antagonizes the hippo pathway. Curr Biol 16:2459–2465PubMedCentralPubMedGoogle Scholar
  97. 97.
    Volodko N, Gordon M, Salla M, Ghazaleh HA, Baksh S (2014) RASSF tumor suppressor gene family: Biological functions and regulation. FEBS Lett 588(16):2671–2684Google Scholar
  98. 98.
    Praskova M, Khoklatchev A, Ortiz-Vega S, Avruch J (2004) Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras. Biochem J 381:453–462PubMedCentralPubMedGoogle Scholar
  99. 99.
    Matallanas D, Romano D, Yee K, Meissl K, Kucerova L, Piazzolla D, Baccarini M, Vass JK, Kolch W, O’neill E (2007) RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein. Mol Cell 27:962–975PubMedCentralPubMedGoogle Scholar
  100. 100.
    Khokhlatchev A, Rabizadeh S, Xavier R, Nedwidek M, Chen T, Zhang XF, Seed B, Avruch J (2002) Identification of a novel Ras-regulated proapoptotic pathway. Curr Biol 12:253–265PubMedGoogle Scholar
  101. 101.
    Cooper WN, Hesson LB, Matallanas D, Dallol A, von Kriegsheim A, Ward R, Kolch W, Latif F (2009) RASSF2 associates with and stabilizes the proapoptotic kinase MST2. Oncogene 28:2988–2998PubMedCentralPubMedGoogle Scholar
  102. 102.
    Song H, Oh S, Oh HJ, Lim DS (2010) Role of the tumor suppressor RASSF2 in regulation of MST1 kinase activity. Biochem Biophys Res Commun 391:969–973PubMedGoogle Scholar
  103. 103.
    Ikeda M, Hirabayashi S, Fujiwara N, Mori H, Kawata A, Iida J, Bao Y, Sato Y, Iida T, Sugimura H, Hata Y (2007) Ras-association domain family protein 6 induces apoptosis via both caspase-dependent and caspase-independent pathways. Exp Cell Res 313:1484–1495PubMedGoogle Scholar
  104. 104.
    Iwasa H, Kudo T, Maimaiti S, Ikeda M, Maruyama J, Nakagawa K, Hata Y (2013) The RASSF6 tumor suppressor protein regulates apoptosis and the cell cycle via MDM2 protein and p53 protein. J Biol Chem 288:30320–30329PubMedCentralPubMedGoogle Scholar
  105. 105.
    Crose LE, Galindo KA, Kephart JG, Chen C, Fitamant J, Bardeesy N, Bentley RC, Galindo RL, Ashley Chi JT, Linardic CM (2014) Alveolar rhabdomyosarcoma-associated PAX3-FOXO1 promotes tumorigenesis via Hippo pathway suppression. J Clin Invest 124(1):285–296Google Scholar
  106. 106.
    Ribeiro PS, Josué F, Wepf A, Wehr MC, Rinner O, Kelly G, Tapon N, Gstaiger M (2010) Combined functional genomic and proteomic approaches identify a PP2A complex as a negative regulator of Hippo signaling. Mol Cell 39:521–534PubMedGoogle Scholar
  107. 107.
    Guo C, Zhang X, Pfeifer GP (2011) The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian STE20-like kinases MST1 and MST2. J Biol Chem 286:6253–6261PubMedCentralPubMedGoogle Scholar
  108. 108.
    Habbig S, Bartram MP, Müller RU, Schwarz R, Andriopoulos N, Chen S, Sägmüller JG, Hoehne M, Burst V, Liebau MC, Reinhardt HC, Benzing T, Schermer B (2011) NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway. J Cell Biol 193:633–642PubMedCentralPubMedGoogle Scholar
  109. 109.
    Habbig S, Bartram MP, Sägmüller JG, Griessmann A, Franke M, Müller RU, Schwarz R, Hoehne M, Bergmann C, Tessmer C, Reinhardt HC, Burst V, Benzing T, Schermer B (2012) The ciliopathy disease protein NPHP9 promotes nuclear delivery and activation of the oncogenic transcriptional regulator TAZ. Hum Mol Genet 21:5528–5538PubMedGoogle Scholar
  110. 110.
    Vigneron AM, Ludwig RL, Vousden KH (2010) Cytoplasmic ASPP1 inhibits apoptosis through the control of YAP. Genes Dev 24:2430–2439PubMedCentralPubMedGoogle Scholar
  111. 111.
    Jeon YH, Park YH, Lee JH, Hong JH, Kim IY (2014) Selenoprotein W enhances skeletal muscle differentiation by inhibiting TAZ binding to 14-3-3 protein. Biochim Biophys Acta 1843:1356–1364PubMedGoogle Scholar
  112. 112.
    Sansores-Garcia L, Atkins M, Moya IM, Shahmoradgoli M, Tao C, Mills GB, Halder G (2013) Mask is required for the activity of the Hippo pathway effector Yki/YAP. Curr Biol 23:229–235PubMedCentralPubMedGoogle Scholar
  113. 113.
    Sidor CM, Brain R, Thompson BJ (2013) Mask proteins are cofactors of Yorkie/YAP in the Hippo pathway. Curr Biol 23:223–228PubMedGoogle Scholar
  114. 114.
    Machado-Neto JA, Lazarini M, Favaro P, Franchi GC, Nowill AE, Saad ST, Traina F (2014) ANKHD1, a novel component of the Hippo signaling pathway, promotes YAP1 activation and cell cycle progression in prostate cancer cells. Exp Cell Res 324:137–145PubMedGoogle Scholar
  115. 115.
    Strano S, Monti O, Pediconi N, Baccarini A, Fontemaggi G, Lapi E, Mantovani F, Damalas A, Citro G, Sacchi A, Del Sal G, Levrero M, Blandino G (2005) The transcriptional coactivator yes-associated protein drives p73 gene-target specificity in response to DNA Damage. Mol Cell 18:447–459PubMedGoogle Scholar
  116. 116.
    Wu H, Xiao Y, Zhang S, Ji S, Wei L, Fan F, Geng J, Tian J, Sun X, Qin F, Jin C, Lin J, Yin ZY, Zhang T, Luo L, Li Y, Song S, Lin SC, Deng X, Camargo F, Avruch J, Chen L, Zhou D (2013) The Ets transcription factor GABP is a component of the hippo pathway essential for growth and antioxidant defense. Cell Rep 3:1663–1677PubMedGoogle Scholar
  117. 117.
    Seo E, Basu-Roy U, Gunaratne PH, Coarfa C, Lim DS, Basilico C, Mansukhani A (2013) SOX2 regulates YAP1 to maintain stemness and determine cell fate in the osteo-adipo lineage. Cell Rep 3:2075–2087PubMedGoogle Scholar
  118. 118.
    Mahoney JE, Mori M, Szymaniak AD, Varelas X, Cardoso WV (2014) The hippo pathway effector yap controls patterning and differentiation of airway epithelial progenitors. Dev Cell 30:137–150PubMedGoogle Scholar
  119. 119.
    Pobbati AV, Hong W (2013) Emerging roles of TEAD transcription factors and its coactivators in cancers. Cancer Biol Ther 14:390–398PubMedCentralPubMedGoogle Scholar
  120. 120.
    Chen L, Chan SW, Zhang X, Walsh M, Lim CJ, Hong W, Song H (2010) Structural basis of YAP recognition by TEAD4 in the hippo pathway. Genes Dev 24:290–300PubMedCentralPubMedGoogle Scholar
  121. 121.
    Li Z, Zhao B, Wang P, Chen F, Dong Z, Yang H, Guan KL, Xu Y (2010) Structural insights into the YAP and TEAD complex. Genes Dev 24:235–240PubMedCentralPubMedGoogle Scholar
  122. 122.
    Tian W, Yu J, Tomchick DR, Pan D, Luo X (2010) Structural and functional analysis of the YAP-binding domain of human TEAD2. Proc Natl Acad Sci USA 107:7293–7298PubMedCentralPubMedGoogle Scholar
  123. 123.
    Mesrouze Y, Hau JC, Erdmann D, Zimmermann C, Fontana P, Schmelzle T, Chène P (2014) The surprising features of the TEAD4-Vgll1 protein-protein interaction. Chem Bio Chem 15:537–542PubMedGoogle Scholar
  124. 124.
    Hau JC, Erdmann D, Mesrouze Y, Furet P, Fontana P, Zimmermann C, Schmelzle T, Hofmann F, Chène P (2013) The TEAD4-YAP/TAZ protein-protein interaction: expected similarities and unexpected differences. Chem Bio Chem 14:1218–1225PubMedGoogle Scholar
  125. 125.
    Koontz LM, Liu-Chittenden Y, Yin F, Zheng Y, Yu J, Huang B, Chen Q, Wu S, Pan D (2013) The Hippo effector Yorkie controls normal tissue growth by antagonizing scalloped-mediated default repression. Dev Cell 25:388–401PubMedCentralPubMedGoogle Scholar
  126. 126.
    Zhang W, Gao Y, Li P, Shi Z, Guo T, Li F, Han X, Feng Y, Zheng C, Wang Z, Chen H, Zhou Z, Zhang L, Ji H (2014) VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex. Cell Res 24:331–343PubMedGoogle Scholar
  127. 127.
    Jiao S, Wang H, Shi Z, Dong A, Zhang W, Song X, He F, Wang Y, Zhang Z, Wang W, Wang X, Guo T, Li P, Zhao Y, Ji H, Zhang L, Zhou Z (2014) A peptide mimicking VGLL4 function acts as a YAP antagonist therapy against gastric cancer. Cancer Cell 25:166–180PubMedGoogle Scholar
  128. 128.
    Alarcón C, Zaromytidou AI, Xi Q, Gao S, Yu J, Fujisawa S, Barlas A, Miller AN, Manova-Todorova K, Macias MJ, Sapkota G, Pan D, Massagué J (2009) Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways. Cell 139:757–769PubMedCentralPubMedGoogle Scholar
  129. 129.
    Fujii M, Nakanishi H, Toyoda T, Tanaka I, Kondo Y, Osada H, Sekido Y (2012) Convergent signaling in the regulation of connective tissue growth factor in malignant mesothelioma: TGFβ signaling and defects in the Hippo signaling cascade. Cell Cycle 11:3373–3379PubMedCentralPubMedGoogle Scholar
  130. 130.
    Mahoney WM, Hong JH, Yaffe MB, Farrance IK (2005) The transcriptional co-activator TAZ interacts differentially with transcriptional enhancer factor-1 (TEF-1) family members. Biochem J 388:217–225PubMedCentralPubMedGoogle Scholar
  131. 131.
    Ferrigno O, Lallemand F, Verrecchia F, L’Hoste S, Camonis J, Atfi A, Mauviel A (2002) Yes-associated protein (YAP65) interacts with Smad7 and potentiates its inhibitory activity against TGF-beta/Smad signaling. Oncogene 21:4879–4884PubMedGoogle Scholar
  132. 132.
    Varelas X, Sakuma R, Samavarchi-Tehrani P, Peerani R, Rao BM, Dembowy J, Yaffe MB, Zandstra PW, Wrana JL (2008) TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal. Nat Cell Biol 10:837–848PubMedGoogle Scholar
  133. 133.
    Varelas X, Samavarchi-Tehrani P, Narimatsu M, Weiss A, Cockburn K, Larsen BG, Rossant J, Wrana JL (2010) The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-β-SMAD pathway. Dev Cell 19:831–844PubMedGoogle Scholar
  134. 134.
    Murakami M, Tominaga J, Makita R, Uchijima Y, Kurihara Y, Nakagawa O, Asano T, Kurihara H (2006) Transcriptional activity of Pax3 is co-activated by TAZ. Biochem Biophys Res Commun 339:533–539PubMedGoogle Scholar
  135. 135.
    Di Palma T, D’Andrea B, Liguori GL, Liguoro A, de Cristofaro T, Del Prete D, Pappalardo A, Mascia A, Zannini M (2009) TAZ is a coactivator for Pax8 and TTF-1, two transcription factors involved in thyroid differentiation. Exp Cell Res 315:162–175PubMedGoogle Scholar
  136. 136.
    Jeong H, Bae S, An SY, Byun MR, Hwang JH, Yaffe MB, Hong JH, Hwang ES (2010) TAZ as a novel enhancer of MyoD-mediated myogenic differentiation. FASEB J 24:3310–3320PubMedGoogle Scholar
  137. 137.
    Hong JH, Hwang ES, McManus MT, Amsterdam A, Tian Y, Kalmukova R, Mueller E, Benjamin T, Spiegelman BM, Sharp PA, Hopkins N, Yaffe MB (2005) TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science 309:1074–1078PubMedGoogle Scholar
  138. 138.
    Vitolo MI, Anglin IE, Mahoney WM, Renoud KJ, Gartenhaus RB, Bachman KE, Passaniti A (2007) The RUNX2 transcription factor cooperates with the YES-associated protein, YAP65, to promote cell transformation. Cancer Biol Ther 6:856–863PubMedGoogle Scholar
  139. 139.
    Zhao R, Fallon TR, Saladi SV, Pardo-Saganta A, Villoria J, Mou H, Vinarsky V, Gonzalez-Celeiro M, Nunna N, Hariri LP, Camargo F, Ellisen LW, Rajagopal J (2014) Yap tunes airway epithelial size and architecture by regulating the identity, maintenance, and self-renewal of stem cells. Dev Cell 30:151–165PubMedGoogle Scholar
  140. 140.
    Chen HI, Einbond A, Kwak SJ, Linn H, Koepf E, Peterson S, Kelly JW, Sudol M (1997) Characterization of the WW domain of human yes-associated protein and its polyproline-containing ligands. J Biol Chem 272:17070–17077PubMedGoogle Scholar
  141. 141.
    Chan SW, Lim CJ, Huang C, Chong YF, Gunaratne HJ, Hogue KA, Blackstock WP, Harvey KF, Hong W (2011) WW domain-mediated interaction with Wbp2 is important for the oncogenic property of TAZ. Oncogene 30:600–610PubMedCentralPubMedGoogle Scholar
  142. 142.
    Zhang X, Milton CC, Poon CL, Hong W, Harvey KF (2011) Wbp2 cooperates with Yorkie to drive tissue growth downstream of the Salvador-Warts-Hippo pathway. Cell Death Differ 18:1346–1355PubMedCentralPubMedGoogle Scholar
  143. 143.
    Kang HS, Beak JY, Kim YS, Herbert R, Jetten AM (2009) Glis3 is associated with primary cilia and Wwtr1/TAZ and implicated in polycystic kidney disease. Mol Cell Biol 29:2556–2569PubMedCentralPubMedGoogle Scholar
  144. 144.
    Shao D, Zhai P, Del Re DP, Sciarretta S, Yabuta N, Nojima H, Lim DS, Pan D, Sadoshima J (2014) A functional interaction between Hippo-YAP signalling and FoxO1 mediates the oxidative stress response. Nat Commun 5:3315PubMedCentralPubMedGoogle Scholar
  145. 145.
    Bendinelli P, Maroni P, Matteucci E, Luzzati A, Perrucchini G, Desiderio MA (2013) Hypoxia inducible factor-1 is activated by transcriptional co-activator with PDZ-binding motif (TAZ) versus WWdomain-containing oxidoreductase (WWOX) in hypoxic microenvironment of bone metastasis from breast cancer. Eur J Cancer 49:2608–2618PubMedGoogle Scholar
  146. 146.
    Chaulk SG, Lattanzi VJ, Hiemer SE, Fahlman RP, Varelas X (2014) The Hippo pathway effectors TAZ/YAP regulate dicer expression and microRNA biogenesis through Let-7. J Biol Chem 289:1886–1891PubMedGoogle Scholar
  147. 147.
    Mori M, Triboulet R, Mohseni M, Schlegelmilch K, Shrestha K, Camargo FD, Gregory RI (2014) Hippo signaling regulates microprocessor and links cell-density-dependent miRNA biogenesis to cancer. Cell 156:893–906PubMedGoogle Scholar
  148. 148.
    Aylon Y, Ofir-Rosenfeld Y, Yabuta N, Lapi E, Nojima H, Lu X, Oren M (2010) The Lats2 tumor suppressor augments p53-mediated apoptosis by promoting the nuclear proapoptotic function of ASPP1. Genes Dev 24:2420–2429PubMedCentralPubMedGoogle Scholar
  149. 149.
    Tsutsumi R, Masoudi M, Takahashi A, Fujii Y, Hayashi T, Kikuchi I, Satou Y, Taira M, Hatakeyama M (2013) YAP and TAZ, Hippo signaling targets, act as a rheostat for nuclear SHP2 function. Dev Cell 26:658–665PubMedGoogle Scholar
  150. 150.
    Azzolin L, Panciera T, Soligo S, Enzo E, Bicciato S, Dupont S, Bresolin S, Frasson C, Basso G, Guzzardo V, Fassina A, Cordenonsi M, Piccolo S (2014) YAP/TAZ incorporation in the β-catenin destruction complex orchestrates the Wnt response. Cell 158(1):157–170Google Scholar
  151. 151.
    Varelas X, Miller BW, Sopko R, Song S, Gregorieff A, Fellouse FA, Sakuma R, Pawson T, Hunziker W, McNeill H, Wrana JL, Attisano L (2010) The Hippo pathway regulates Wnt/beta-catenin signaling. Dev Cell 18:579–591PubMedGoogle Scholar
  152. 152.
    Barry ER, Morikawa T, Butler BL, Shrestha K, de la Rosa R, Yan KS, Fuchs CS, Magness ST, Smits R, Ogino S, Kuo CJ, Camargo FD (2013) Restriction of intestinal stem cell expansion and the regenerative response by YAP. Nature 493:106–110PubMedCentralPubMedGoogle Scholar
  153. 153.
    Imajo M, Miyatake K, Iimura A, Miyamoto A, Nishida E (2012) A molecular mechanism that links Hippo signalling to the inhibition of Wnt/β-catenin signalling. EMBO J 31:1109–1122PubMedCentralPubMedGoogle Scholar
  154. 154.
    Camargo FD, Gokhale S, Johnnidis JB, Fu D, Bell GW, Jaenisch R, Brummelkamp TR (2007) YAP1 increases organ size and expands undifferentiated progenitor cells. Curr Biol 17:2054–2060PubMedGoogle Scholar
  155. 155.
    Heallen T, Zhang M, Wang J, Bonilla-Claudio M, Klysik E, Johnson RL, Martin JF (2011) Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size. Science 332:458–461PubMedCentralPubMedGoogle Scholar
  156. 156.
    Zhou D, Zhang Y, Wu H, Barry E, Yin Y, Lawrence E, Dawson D, Willis JE, Markowitz SD, Camargo FD, Avruch J (2011) Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. Proc Natl Acad Sci USA 108:E1312–E1320PubMedCentralPubMedGoogle Scholar
  157. 157.
    Cai J, Zhang N, Zheng Y, de Wilde RF, Maitra A, Pan D (2010) The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program. Genes Dev 24:2383–2388PubMedCentralPubMedGoogle Scholar
  158. 158.
    Azzolin L, Zanconato F, Bresolin S, Forcato M, Basso G, Bicciato S, Cordenonsi M, Piccolo S (2012) Role of TAZ as mediator of Wnt signaling. Cell 151:1443–1456PubMedGoogle Scholar
  159. 159.
    Wang J, Park JS, Wei Y, Rajurkar M, Cotton JL, Fan Q, Lewis BC, Ji H, Mao J (2013) TRIB2 acts downstream of Wnt/TCF in liver cancer cells to regulate YAP and C/EBPα function. Mol Cell 51:211–225PubMedCentralPubMedGoogle Scholar
  160. 160.
    Byun MR, Hwang JH, Kim AR, Kim KM, Hwang ES, Yaffe MB, Hong JH (2014) Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation. Cell Death Differ 21:854–863PubMedGoogle Scholar
  161. 161.
    Fernandez-L A, Northcott PA, Dalton J, Fraga C, Ellison D, Angers S, Taylor MD, Kenney AM (2009) YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog-driven neural precursor proliferation. Genes Dev 23:2729–2741PubMedCentralPubMedGoogle Scholar
  162. 162.
    Lin YT, Ding JY, Li MY, Yeh TS, Wang TW, Yu JY (2012) YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway. Exp Cell Res 318:1877–1888PubMedGoogle Scholar
  163. 163.
    Tschaharganeh DF, Chen X, Latzko P, Malz M, Gaida MM, Felix K, Ladu S, Singer S, Pinna F, Gretz N, Sticht C, Tomasi ML, Delogu S, Evert M, Fan B, Ribback S, Jiang L, Brozzetti S, Bergmann F, Dombrowski F, Schirmacher P, Calvisi DF, Breuhahn K (2013) Yes-associated protein up-regulates Jagged-1 and activates the Notch pathway in human hepatocellular carcinoma. Gastroenterology 144(1530–1542):e1512Google Scholar
  164. 164.
    Zhang J, Ji JY, Yu M, Overholtzer M, Smolen GA, Wang R, Brugge JS, Dyson NJ, Haber DA (2009) YAP-dependent induction of amphiregulin identifies a non-cell-autonomous component of the Hippo pathway. Nat Cell Biol 11:1444–1450PubMedCentralPubMedGoogle Scholar
  165. 165.
    Yang N, Morrison CD, Liu P, Miecznikowski J, Bshara W, Han S, Zhu Q, Omilian AR, Li X, Zhang J (2012) TAZ induces growth factor-independent proliferation through activation of EGFR ligand amphiregulin. Cell Cycle 11:2922–2930PubMedCentralPubMedGoogle Scholar
  166. 166.
    Ding L, Ellis MJ, Li S, Larson DE, Chen K, Wallis JW, Harris CC, McLellan MD, Fulton RS, Fulton LL, Abbott RM, Hoog J, Dooling DJ, Koboldt DC, Schmidt H, Kalicki J, Zhang Q, Chen L, Lin L, Wendl MC, McMichael JF, Magrini VJ, Cook L, McGrath SD, Vickery TL, Appelbaum E, Deschryver K, Davies S, Guintoli T, Crowder R, Tao Y, Snider JE, Smith SM, Dukes AF, Sanderson GE, Pohl CS, Delehaunty KD, Fronick CC, Pape KA, Reed JS, Robinson JS, Hodges JS, Schierding W, Dees ND, Shen D, Locke DP, Wiechert ME, Eldred JM, Peck JB, Oberkfell BJ, Lolofie JT, Du F, Hawkins AE, O’Laughlin MD, Bernard KE, Cunningham M, Elliott G, Mason MD, Thompson DM, Ivanovich JL, Goodfellow PJ, Perou CM, Weinstock GM, Aft R, Watson M, Ley TJ, Wilson RK, Mardis ER (2010) Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 464:999–1005PubMedCentralPubMedGoogle Scholar
  167. 167.
    Williamson KA, Rainger J, Floyd JA, Ansari M, Meynert A, Aldridge KV, Rainger JK, Anderson CA, Moore AT, Hurles ME, Clarke A, van Heyningen V, Verloes A, Taylor, Wilkie AO, Fitzpatrick, Consortium UK (2014) Heterozygous loss-of-function mutations in YAP1 cause both isolated and syndromic optic fissure closure defects. Am J Hum Genet 94:295–302PubMedCentralPubMedGoogle Scholar
  168. 168.
    Errani C, Zhang L, Sung YS, Hajdu M, Singer S, Maki RG, Healey JH, Antonescu CR (2011) A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. Genes Chromosomes Cancer 50:644–653PubMedCentralPubMedGoogle Scholar
  169. 169.
    Antonescu CR, Le Loarer F, Mosquera JM, Sboner A, Zhang L, Chen CL, Chen HW, Pathan N, Krausz T, Dickson BC, Weinreb I, Rubin MA, Hameed M, Fletcher CD (2013) Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma. Genes Chromosomes Cancer 52:775–784PubMedCentralPubMedGoogle Scholar
  170. 170.
    Zhao B, Kim J, Ye X, Lai ZC, Guan KL (2009) Both TEAD-binding and WW domains are required for the growth stimulation and oncogenic transformation activity of yes-associated protein. Cancer Res 69:1089–1098PubMedGoogle Scholar
  171. 171.
    Chan SW, Lim CJ, Loo LS, Chong YF, Huang C, Hong W (2009) TEADs mediate nuclear retention of TAZ to promote oncogenic transformation. J Biol Chem 284:14347–14358PubMedCentralPubMedGoogle Scholar
  172. 172.
    Zhao B, Ye X, Yu J, Li L, Li W, Li S, Lin JD, Wang CY, Chinnaiyan AM, Lai ZC, Guan KL (2008) TEAD mediates YAP-dependent gene induction and growth control. Genes Dev 22:1962–1971PubMedCentralPubMedGoogle Scholar
  173. 173.
    Lamar JM, Stern P, Liu H, Schindler JW, Jiang ZG, Hynes RO (2012) The Hippo pathway target, YAP, promotes metastasis through its TEAD-interaction domain. Proc Natl Acad Sci USA 109:E2441–E2450PubMedCentralPubMedGoogle Scholar
  174. 174.
    Kapoor A, Yao W, Ying H, Hua S, Liewen A, Wang Q, Zhong Y, Wu CJ, Sadanandam A, Hu B, Chang Q, Chu GC, Al-Khalil R, Jiang S, Xia H, Fletcher-Sananikone E, Lim C, Horwitz GI, Viale A, Pettazzoni P, Sanchez N, Wang H, Protopopov A, Zhang J, Heffernan T, Johnson RL, Chin L, Wang YA, Draetta G, DePinho RA (2014) Yap1 activation enables bypass of oncogenic kras addiction in pancreatic cancer. Cell 158(1):185–197Google Scholar
  175. 175.
    Shao DD, Xue W, Krall EB, Bhutkar A, Piccioni F, Wang X, Schinzel AC, Sood S, Rosenbluh J, Kim JW, Zwang Y, Roberts TM, Root DE, Jacks T, Hahn WC (2014) KRAS and YAP1 converge to regulate EMT and tumor survival. Cell 158(1):171–184Google Scholar
  176. 176.
    Zhang H, Liu CY, Zha ZY, Zhao B, Yao J, Zhao S, Xiong Y, Lei QY, Guan KL (2009) TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition. J Biol Chem 284:13355–13362PubMedCentralPubMedGoogle Scholar
  177. 177.
    Lai D, Ho KC, Hao Y, Yang X (2011) Taxol resistance in breast cancer cells is mediated by the hippo pathway component TAZ and its downstream transcriptional targets Cyr61 and CTGF. Cancer Res 71:2728–2738PubMedGoogle Scholar
  178. 178.
    Zhang W, Nandakumar N, Shi Y, Manzano M, Smith A, Graham G, Gupta S, Vietsch EE, Laughlin SZ, Wadhwa M, Chetram M, Joshi M, Wang F, Kallakury B, Toretsky J, Wellstein A, Yi C (2014) Downstream of mutant KRAS, the transcription regulator YAP is essential for neoplastic progression to pancreatic ductal adenocarcinoma. Sci Signal 7:ra42PubMedCentralPubMedGoogle Scholar
  179. 179.
    Xu MZ, Chan SW, Liu AM, Wong KF, Fan ST, Chen J, Poon RT, Zender L, Lowe SW, Hong W, Luk JM (2011) AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma. Oncogene 30:1229–1240PubMedCentralPubMedGoogle Scholar
  180. 180.
    Tumaneng K, Schlegelmilch K, Russell RC, Yimlamai D, Basnet H, Mahadevan N, Fitamant J, Bardeesy N, Camargo FD, Guan KL (2012) YAP mediates crosstalk between the Hippo and PI(3)K–TOR pathways by suppressing PTEN via miR-29. Nat Cell Biol 14:1322–1329PubMedCentralPubMedGoogle Scholar
  181. 181.
    Song S, Ajani JA, Honjo S, Maru DM, Chen Q, Scott AW, Heallen TR, Xiao L, Hofstetter WL, Weston B, Lee JH, Wadhwa R, Sudo K, Stroehlein JR, Martin JF, Hung MC, Johnson RL (2014) Hippo coactivator YAP1 upregulates SOX9 and endows stem-like properties to esophageal cancer cells. Cancer Res 74(15):4170–4182Google Scholar
  182. 182.
    Bhat KP, Salazar KL, Balasubramaniyan V, Wani K, Heathcock L, Hollingsworth F, James JD, Gumin J, Diefes KL, Kim SH, Turski A, Azodi Y, Yang Y, Doucette T, Colman H, Sulman EP, Lang FF, Rao G, Copray S, Vaillant BD, Aldape KD (2011) The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant glioma. Genes Dev 25:2594–2609PubMedCentralPubMedGoogle Scholar
  183. 183.
    Liu-Chittenden Y, Huang B, Shim JS, Chen Q, Lee SJ, Anders RA, Liu JO, Pan D (2012) Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. Genes Dev 26:1300–1305PubMedCentralPubMedGoogle Scholar
  184. 184.
    Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715PubMedCentralPubMedGoogle Scholar
  185. 185.
    Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A, Frasson C, Inui M, Montagner M, Parenti AR, Poletti A, Daidone MG, Dupont S, Basso G, Bicciato S, Piccolo S (2011) The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell 147:759–772PubMedGoogle Scholar
  186. 186.
    Ganem NJ, Cornils H, Chiu SY, O’Rourke KP, Arnaud J, Yimlamai D, Théry M, Camargo FD, Pellman D (2014) Cytokinesis failure triggers hippo tumor suppressor pathway activation. Cell 158:833–848PubMedGoogle Scholar
  187. 187.
    Yuan M, Tomlinson V, Lara R, Holliday D, Chelala C, Harada T, Gangeswaran R, Manson-Bishop C, Smith P, Danovi SA, Pardo O, Crook T, Mein CA, Lemoine NR, Jones LJ, Basu S (2008) Yes-associated protein (YAP) functions as a tumor suppressor in breast. Cell Death Differ 15:1752–1759PubMedGoogle Scholar
  188. 188.
    Ehsanian R, Brown M, Lu H, Yang XP, Pattatheyil A, Yan B, Duggal P, Chuang R, Doondeea J, Feller S, Sudol M, Chen Z, Van Waes C (2010) YAP dysregulation by phosphorylation or ΔNp63-mediated gene repression promotes proliferation, survival and migration in head and neck cancer subsets. Oncogene 29:6160–6171PubMedCentralPubMedGoogle Scholar
  189. 189.
    Cottini F, Hideshima T, Xu C, Sattler M, Dori M, Agnelli L, Ten Hacken E, Bertilaccio MT, Antonini E, Neri A, Ponzoni M, Marcatti M, Richardson PG, Carrasco R, Kimmelman AC, Wong KK, Caligaris-Cappio F, Blandino G, Kuehl WM, Anderson KC, Tonon G (2014) Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers. Nat Med 20:599–606PubMedCentralPubMedGoogle Scholar
  190. 190.
    Morin-Kensicki EM, Boone BN, Howell M, Stonebraker JR, Teed J, Alb JG, Magnuson TR, O’Neal W, Milgram SL (2006) Defects in yolk sac vasculogenesis, chorioallantoic fusion, and embryonic axis elongation in mice with targeted disruption of Yap65. Mol Cell Biol 26:77–87PubMedCentralPubMedGoogle Scholar
  191. 191.
    Kaneko KJ, DePamphilis ML (1998) Regulation of gene expression at the beginning of mammalian development and the TEAD family of transcription factors. Dev Genet 22:43–55PubMedGoogle Scholar
  192. 192.
    Yagi R, Kohn MJ, Karavanova I, Kaneko KJ, Vullhorst D, DePamphilis ML, Buonanno A (2007) Transcription factor TEAD4 specifies the trophectoderm lineage at the beginning of mammalian development. Development 134:3827–3836PubMedGoogle Scholar
  193. 193.
    Ota M, Sasaki H (2008) Mammalian Tead proteins regulate cell proliferation and contact inhibition as transcriptional mediators of Hippo signaling. Development 135:4059–4069PubMedGoogle Scholar
  194. 194.
    Nishioka N, Inoue K, Adachi K, Kiyonari H, Ota M, Ralston A, Yabuta N, Hirahara S, Stephenson RO, Ogonuki N, Makita R, Kurihara H, Morin-Kensicki EM, Nojima H, Rossant J, Nakao K, Niwa H, Sasaki H (2009) The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass. Dev Cell 16:398–410PubMedGoogle Scholar
  195. 195.
    Hirate Y, Hirahara S, Inoue K, Suzuki A, Alarcon VB, Akimoto K, Hirai T, Hara T, Adachi M, Chida K, Ohno S, Marikawa Y, Nakao K, Shimono A, Sasaki H (2013) Polarity-dependent distribution of angiomotin localizes Hippo signaling in preimplantation embryos. Curr Biol 23:1181–1194PubMedCentralPubMedGoogle Scholar
  196. 196.
    Cockburn K, Biechele S, Garner J, Rossant J (2013) The Hippo pathway member Nf2 is required for inner cell mass specification. Curr Biol 23:1195–1201PubMedGoogle Scholar
  197. 197.
    Lorthongpanich C, Messerschmidt DM, Chan SW, Hong W, Knowles BB, Solter D (2013) Temporal reduction of LATS kinases in the early preimplantation embryo prevents ICM lineage differentiation. Genes Dev 27:1441–1446PubMedCentralPubMedGoogle Scholar
  198. 198.
    Lian I, Kim J, Okazawa H, Zhao J, Zhao B, Yu J, Chinnaiyan A, Israel MA, Goldstein LS, Abujarour R, Ding S, Guan KL (2010) The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation. Genes Dev 24:1106–1118PubMedCentralPubMedGoogle Scholar
  199. 199.
    Beyer TA, Weiss A, Khomchuk Y, Huang K, Ogunjimi AA, Varelas X, Wrana JL (2013) Switch enhancers interpret TGF-β and Hippo signaling to control cell fate in human embryonic stem cells. Cell Rep 5:1611–1624PubMedGoogle Scholar
  200. 200.
    Qin H, Blaschke K, Wei G, Ohi Y, Blouin L, Qi Z, Yu J, Yeh RF, Hebrok M, Ramalho-Santos M (2012) Transcriptional analysis of pluripotency reveals the Hippo pathway as a barrier to reprogramming. Hum Mol Genet 21:2054–2067PubMedCentralPubMedGoogle Scholar
  201. 201.
    Allen HF, Wade PA, Kutateladze TG (2013) The NuRD architecture. Cell Mol Life Sci 70:3513–3524PubMedCentralPubMedGoogle Scholar
  202. 202.
    Xin M, Kim Y, Sutherland LB, Murakami M, Qi X, McAnally J, Porrello ER, Mahmoud AI, Tan W, Shelton JM, Richardson JA, Sadek HA, Bassel-Duby R, Olson EN (2013) Hippo pathway effector Yap promotes cardiac regeneration. Proc Natl Acad Sci USA 110:13839–13844PubMedCentralPubMedGoogle Scholar
  203. 203.
    Gao T, Zhou D, Yang C, Singh T, Penzo-Méndez A, Maddipati R, Tzatsos A, Bardeesy N, Avruch J, Stanger BZ (2013) Hippo signaling regulates differentiation and maintenance in the exocrine pancreas. Gastroenterology 144:1543–1553PubMedCentralPubMedGoogle Scholar
  204. 204.
    George NM, Day CE, Boerner BP, Johnson RL, Sarvetnick NE (2012) Hippo signaling regulates pancreas development through inactivation of Yap. Mol Cell Biol 32:5116–5128PubMedCentralPubMedGoogle Scholar
  205. 205.
    Dong J, Feldmann G, Huang J, Wu S, Zhang N, Comerford SA, Gayyed MF, Anders RA, Maitra A, Pan D (2007) Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell 130:1120–1133PubMedCentralPubMedGoogle Scholar
  206. 206.
    Lee KP, Lee JH, Kim TS, Kim TH, Park HD, Byun JS, Kim MC, Jeong WI, Calvisi DF, Kim JM, Lim DS (2010) The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis. Proc Natl Acad Sci USA 107:8248–8253PubMedCentralPubMedGoogle Scholar
  207. 207.
    Lu L, Li Y, Kim SM, Bossuyt W, Liu P, Qiu Q, Wang Y, Halder G, Finegold MJ, Lee JS, Johnson RL (2010) Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver. Proc Natl Acad Sci USA 107:1437–1442PubMedCentralPubMedGoogle Scholar
  208. 208.
    Zhou D, Conrad C, Xia F, Park JS, Payer B, Yin Y, Lauwers GY, Thasler W, Lee JT, Avruch J, Bardeesy N (2009) Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer Cell 16:425–438PubMedCentralPubMedGoogle Scholar
  209. 209.
    Bai H, Zhang N, Xu Y, Chen Q, Khan M, Potter JJ, Nayar SK, Cornish T, Alpini G, Bronk S, Pan D, Anders RA (2012) Yes-associated protein regulates the hepatic response after bile duct ligation. Hepatology 56:1097–1107PubMedCentralPubMedGoogle Scholar
  210. 210.
    Grijalva J, Huizenga M, Mueller K, Rodriguez S, Brazzo J, Camargo F, Sadri-Vakili G, Vakili K (2014) Dynamic alterations in Hippo signaling pathway and YAP activation during liver regeneration. Am J Physiol Gastrointest Liver Physiol 307(2):G196–204Google Scholar
  211. 211.
    Yimlamai D, Christodoulou C, Galli GG, Yanger K, Pepe-Mooney B, Gurung B, Shrestha K, Cahan P, Stanger BZ, Camargo FD (2014) Hippo pathway activity influences liver cell fate. Cell 157:1324–1338PubMedGoogle Scholar
  212. 212.
    Matsui Y, Nakano N, Shao D, Gao S, Luo W, Hong C, Zhai P, Holle E, Yu X, Yabuta N, Tao W, Wagner T, Nojima H, Sadoshima J (2008) Lats2 is a negative regulator of myocyte size in the heart. Circ Res 103:1309–1318PubMedCentralPubMedGoogle Scholar
  213. 213.
    von Gise A, Lin Z, Schlegelmilch K, Honor LB, Pan GM, Buck JN, Ma Q, Ishiwata T, Zhou B, Camargo FD, Pu WT (2012) YAP1, the nuclear target of Hippo signaling, stimulates heart growth through cardiomyocyte proliferation but not hypertrophy. Proc Natl Acad Sci USA 109:2394–2399Google Scholar
  214. 214.
    Del Re DP, Matsuda T, Zhai P, Gao S, Clark GJ, Van Der Weyden L, Sadoshima J (2010) Proapoptotic Rassf1A/Mst1 signaling in cardiac fibroblasts is protective against pressure overload in mice. J Clin Invest 120:3555–3567PubMedCentralPubMedGoogle Scholar
  215. 215.
    Lin Z, von Gise A, Zhou P, Gu F, Ma Q, Jiang J, Yau AL, Buck JN, Gouin KA, van Gorp PR, Zhou B, Chen J, Seidman JG, Wang DZ, Pu WT (2014) Cardiac-specific YAP activation improves cardiac function and survival in an experimental murine myocardial infarction model. Circ Res 115(3):354–363Google Scholar
  216. 216.
    Xin M, Kim Y, Sutherland LB, Qi X, McAnally J, Schwartz RJ, Richardson JA, Bassel-Duby R, Olson EN (2011) Regulation of insulin-like growth factor signaling by Yap governs cardiomyocyte proliferation and embryonic heart size. Sci Signal 4:ra70PubMedCentralPubMedGoogle Scholar
  217. 217.
    Chen SN, Gurha P, Lombardi R, Ruggiero A, Willerson JT, Marian AJ (2014) The Hippo pathway is activated and is a causal mechanism for adipogenesis in arrhythmogenic cardiomyopathy. Circ Res 114(3):454–468Google Scholar
  218. 218.
    Zhang H, Pasolli HA, Fuchs E (2011) Yes-associated protein (YAP) transcriptional coactivator functions in balancing growth and differentiation in skin. Proc Natl Acad Sci USA 108:2270–2275PubMedCentralPubMedGoogle Scholar
  219. 219.
    Beverdam A, Claxton C, Zhang X, James G, Harvey KF, Key B (2013) Yap controls stem/progenitor cell proliferation in the mouse postnatal epidermis. J Invest Dermatol 133:1497–1505PubMedGoogle Scholar
  220. 220.
    Lee MJ, Ran Byun M, Furutani-Seiki M, Hong JH, Jung HS (2014) YAP and TAZ regulate skin wound healing. J Invest Dermatol 134:518–525PubMedGoogle Scholar
  221. 221.
    Cao X, Pfaff SL, Gage FH (2008) YAP regulates neural progenitor cell number via the TEA domain transcription factor. Genes Dev 22:3320–3334PubMedCentralPubMedGoogle Scholar
  222. 222.
    Lavado A, He Y, Paré J, Neale G, Olson EN, Giovannini M, Cao X (2013) Tumor suppressor Nf2 limits expansion of the neural progenitor pool by inhibiting Yap/Taz transcriptional coactivators. Development 140:3323–3334PubMedCentralPubMedGoogle Scholar
  223. 223.
    Li N, Lim G, Chen L, McCabe MF, Kim H, Zhang S, Mao J (2013) Spinal expression of Hippo signaling components YAP and TAZ following peripheral nerve injury in rats. Brain Res 1535:137–147PubMedGoogle Scholar
  224. 224.
    Byun MR, Jeong H, Bae SJ, Kim AR, Hwang ES, Hong JH (2012) TAZ is required for the osteogenic and anti-adipogenic activities of kaempferol. Bone 50:364–372PubMedGoogle Scholar
  225. 225.
    An Y, Kang Q, Zhao Y, Hu X, Li N (2013) Lats2 modulates adipocyte proliferation and differentiation via hippo signaling. PLoS ONE 8:e72042PubMedCentralPubMedGoogle Scholar
  226. 226.
    Jang EJ, Jeong H, Kang JO, Kim NJ, Kim MS, Choi SH, Yoo SE, Hong JH, Bae MA, Hwang ES (2012) TM-25659 enhances osteogenic differentiation and suppresses adipogenic differentiation by modulating the transcriptional co-activator TAZ. Br J Pharmacol 165:1584–1594PubMedCentralPubMedGoogle Scholar
  227. 227.
    Ribas R, Moncaut N, Siligan C, Taylor K, Cross JW, Rigby PW, Carvajal JJ (2011) Members of the TEAD family of transcription factors regulate the expression of Myf5 in ventral somitic compartments. Dev Biol 355:372–380PubMedCentralPubMedGoogle Scholar
  228. 228.
    Benhaddou A, Keime C, Ye T, Morlon A, Michel I, Jost B, Mengus G, Davidson I (2012) Transcription factor TEAD4 regulates expression of myogenin and the unfolded protein response genes during C2C12 cell differentiation. Cell Death Differ 19:220–231PubMedCentralPubMedGoogle Scholar
  229. 229.
    Milewski RC, Chi NC, Li J, Brown C, Lu MM, Epstein JA (2004) Identification of minimal enhancer elements sufficient for Pax3 expression in neural crest and implication of Tead2 as a regulator of Pax3. Development 131:829–837PubMedGoogle Scholar
  230. 230.
    Watt KI, Judson R, Medlow P, Reid K, Kurth TB, Burniston JG, Ratkevicius A, De Bari C, Wackerhage H (2010) Yap is a novel regulator of C2C12 myogenesis. Biochem Biophys Res Commun 393:619–624PubMedGoogle Scholar
  231. 231.
    Judson RN, Tremblay AM, Knopp P, White RB, Urcia R, De Bari C, Zammit PS, Camargo FD, Wackerhage H (2012) The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells. J Cell Sci 125:6009–6019PubMedCentralPubMedGoogle Scholar
  232. 232.
    Judson RN, Gray SR, Walker C, Carroll AM, Itzstein C, Lionikas A, Zammit PS, De Bari C, Wackerhage H (2013) Constitutive expression of Yes-associated protein (Yap) in adult skeletal muscle fibres induces muscle atrophy and myopathy. PLoS ONE 8:e59622PubMedCentralPubMedGoogle Scholar
  233. 233.
    Bertrand AT, Ziaei S, Ehret C, Duchemin H, Mamchaoui K, Bigot A, Mayer M, Quijano-Roy S, Desguerre I, Lainé J, Ben Yaou R, Bonne G, Coirault C (2014) Cellular microenvironments reveal defective mechanosensing responses and elevated YAP signaling in LMNA-mutated muscle precursors. J Cell Sci 127:2873–2884PubMedGoogle Scholar
  234. 234.
    Yang Z, Nakagawa K, Sarkar A, Maruyama J, Iwasa H, Bao Y, Ishigami-Yuasa M, Ito S, Kagechika H, Hata S, Nishina H, Abe S, Kitagawa M, Hata Y (2014) Screening with a novel cell-based assay for TAZ activators identifies a compound that enhances myogenesis in C2C12 cells and facilitates muscle repair in a muscle injury model. Mol Cell Biol 34:1607–1621PubMedCentralPubMedGoogle Scholar
  235. 235.
    Park GH, Jeong H, Jeong MG, Jang EJ, Bae MA, Lee YL, Kim NJ, Hong JH, Hwang ES (2014) Novel TAZ modulators enhance myogenic differentiation and muscle regeneration. Br J Pharmacol 171(17):4051–4061Google Scholar
  236. 236.
    Enger TB, Samad-Zadeh A, Bouchie MP, Skarstein K, Galtung HK, Mera T, Walker J, Menko AS, Varelas X, Faustman DL, Jensen JL, Kukuruzinska MA (2013) The Hippo signaling pathway is required for salivary gland development and its dysregulation is associated with Sjogren’s syndrome. Lab Invest 93:1203–1218PubMedGoogle Scholar
  237. 237.
    Kawamura K, Cheng Y, Suzuki N, Deguchi M, Sato Y, Takae S, Ho CH, Kawamura N, Tamura M, Hashimoto S, Sugishita Y, Morimoto Y, Hosoi Y, Yoshioka N, Ishizuka B, Hsueh AJ (2013) Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci USA 110:17474–17479PubMedCentralPubMedGoogle Scholar
  238. 238.
    Kwon Y, Vinayagam A, Sun X, Dephoure N, Gygi SP, Hong P, Perrimon N (2013) The Hippo signaling pathway interactome. Science 342:737–740PubMedCentralPubMedGoogle Scholar
  239. 239.
    Wang W, Li X, Huang J, Feng L, Dolinta KG, Chen J (2014) Defining the protein-protein interaction network of the human hippo pathway. Mol Cell Proteomics 13:119–131PubMedGoogle Scholar
  240. 240.
    Couzens AL, Knight JD, Kean MJ, Teo G, Weiss A, Dunham WH, Lin ZY, Bagshaw RD, Sicheri F, Pawson T, Wrana JL, Choi H, Gingras AC (2013) Protein interaction network of the Mammalian hippo pathway reveals mechanisms of kinase-phosphatase interactions. Sci Signal 6:rs15PubMedGoogle Scholar
  241. 241.
    Hauri S, Wepf A, van Drogen A, Varjosalo M, Tapon N, Aebersold R, Gstaiger M (2013) Interaction proteome of human Hippo signaling: modular control of the co-activator YAP1. Mol Syst Biol 9:713PubMedCentralPubMedGoogle Scholar
  242. 242.
    Kohli P, Bartram MP, Habbig S, Pahmeyer C, Lamkemeyer T, Benzing T, Schermer B, Rinschen MM (2014) Label-free quantitative proteomic analysis of the YAP/TAZ interactome. Am J Physiol Cell Physiol 306:C805–C818PubMedGoogle Scholar

Copyright information

© Springer Basel 2014

Authors and Affiliations

  1. 1.Department of Medical Biochemistry, Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan
  2. 2.Center for Brain Integration ResearchTokyo Medical and Dental UniversityTokyoJapan

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