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Cancer Chemotherapy and Pharmacology

, Volume 81, Issue 5, pp 797–808 | Cite as

Targeting the neddylation pathway in cells as a potential therapeutic approach for diseases

  • Jie Ying
  • Miaomiao Zhang
  • Xiaoyan Qiu
  • Yu Lu
Review Article

Abstract

The ubiquitin–proteasome system (UPS) is an important system that regulates the balance of intracellular proteins, and it is involved in the regulation of multiple vital biological processes. The approval of bortezomib for relapsed and refractory multiple myeloma has proven that agents targeting the UPS have the potential to be effective treatment strategies for diseases. Among of all of the components of the UPS, cullin-RING ligases (CRLs) are the focus of research. CRLs are the largest family of ubiquitin E3 ligases and they play a critical role in substrate binding. CRL activity is modulated by many pathways in which neddylation modification is the essential process for cullin activation. Thus, targeting the neddylation pathway of cullins could indirectly affect CRL activity, thereby interfering with substrate protein ubiquitination. In addition to cullin proteins, there are some other target proteins of neddylation, such as p53, mouse double minute 2, and epidermal growth factor receptor. For target proteins, neddylation modification mainly causes functions changes, not degradation. In addition, the level of neddylation is also closely related to disease development and prognosis. In this review, we summarize the research on some target proteins and active target agents of neddylation pathways, and explore the role of neddylation in disease therapy. We came to the conclusion that conducting research on neddylation may be a potential approach to discover some novel targets and agents that could be effective without serious side effects.

Keywords

Neddylation NEDD8 NAE P53 Cullin Disease therapy 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    Haglund K, Dikic I (2005) Ubiquitylation and cell signaling. EMBO J 24(19):3353–3359.  https://doi.org/10.1038/sj.emboj.7600808 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Tsukamoto S (2016) Search for inhibitors of the ubiquitin–proteasome system from natural sources for cancer therapy. Chem Pharm Bull 64(2):112–118.  https://doi.org/10.1248/cpb.c15-00768 CrossRefPubMedGoogle Scholar
  3. 3.
    Glorian V, Allegre J, Berthelet J, Dumetier B, Boutanquoi PM, Droin N, Kayaci C, Cartier J, Gemble S, Marcion G, Gonzalez D, Boidot R, Garrido C, Michaud O, Solary E, Dubrez L (2017) DNA damage and S phase-dependent E2F1 stabilization requires the cIAP1 E3-ubiquitin ligase and is associated with K63-poly-ubiquitination on lysine 161/164 residues. Cell Death Dis 8(5):e2816.  https://doi.org/10.1038/cddis.2017.222 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Zhao Y, Morgan MA, Sun Y (2014) Targeting Neddylation pathways to inactivate cullin-RING ligases for anticancer therapy. Antioxid Redox Signal 21(17):2383–2400.  https://doi.org/10.1089/ars.2013.5795 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Xirodimas DP (2008) Novel substrates and functions for the ubiquitin-like molecule NEDD8. Biochem Soc Trans 36(Pt 5):802–806.  https://doi.org/10.1042/BST0360802 CrossRefPubMedGoogle Scholar
  6. 6.
    Rabut G, Peter M (2008) Function and regulation of protein neddylation. ‘Protein modifications: beyond the usual suspects’ review series. EMBO Rep 9(10):969–976.  https://doi.org/10.1038/embor.2008.183 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Mendoza HM, Shen LN, Botting C, Lewis A, Chen J, Ink B, Hay RT (2003) NEDP1, a highly conserved cysteine protease that deNEDDylates Cullins. J Biol Chem 278(28):25637–25643.  https://doi.org/10.1074/jbc.M212948200 CrossRefPubMedGoogle Scholar
  8. 8.
    Wu K, Yamoah K, Dolios G, Gan-Erdene T, Tan P, Chen A, Lee CG, Wei N, Wilkinson KD, Wang R, Pan ZQ (2003) DEN1 is a dual function protease capable of processing the C terminus of Nedd8 and deconjugating hyper-neddylated CUL1. J Biol Chem 278(31):28882–28891.  https://doi.org/10.1074/jbc.M302888200 CrossRefPubMedGoogle Scholar
  9. 9.
    Huang DT, Ayrault O, Hunt HW, Taherbhoy AM, Duda DM, Scott DC, Borg LA, Neale G, Murray PJ, Roussel MF, Schulman BA (2009) E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification. Mol Cell 33(4):483–495.  https://doi.org/10.1016/j.molcel.2009.01.011 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Oved S, Mosesson Y, Zwang Y, Santonico E, Shtiegman K, Marmor MD, Kochupurakkal BS, Katz M, Lavi S, Cesareni G, Yarden Y (2006) Conjugation to Nedd8 instigates ubiquitylation and down-regulation of activated receptor tyrosine kinases. J Biol Chem 281(31):21640–21651.  https://doi.org/10.1074/jbc.M513034200 CrossRefPubMedGoogle Scholar
  11. 11.
    Lee M-H, Zhao R, Phan L, Yeung S-CJ (2011) Roles of COP9 signalosome in cancer. Cell Cycle 10(18):3057–3066.  https://doi.org/10.4161/cc.10.18.17320 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Xirodimas DP, Saville MK, Bourdon JC, Hay RT, Lane DP (2004) Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity. Cell 118(1):83–97.  https://doi.org/10.1016/j.cell.2004.06.016 CrossRefPubMedGoogle Scholar
  13. 13.
    Stickle NH, Chung J, Klco JM, Hill RP, Kaelin WG, Ohh M (2004) pVHL modification by NEDD8 is required for fibronectin matrix assembly and suppression of tumor development. Mol Cell Biol 24(8):3251–3261.  https://doi.org/10.1128/mcb.24.8.3251-3261.2004 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Embade N, Fernandez-Ramos D, Varela-Rey M, Beraza N, Sini M, Gutierrez de Juan V, Woodhoo A, Martinez-Lopez N, Rodriguez-Iruretagoyena B, Bustamante FJ, de la Hoz AB, Carracedo A, Xirodimas DP, Rodriguez MS, Lu SC, Mato JM, Martinez-Chantar ML (2012) Murine double minute 2 regulates Hu antigen R stability in human liver and colon cancer through NEDDylation. Hepatology 55(4):1237–1248.  https://doi.org/10.1002/hep.24795 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Xirodimas DP, Sundqvist A, Nakamura A, Shen L, Botting C, Hay RT (2008) Ribosomal proteins are targets for the NEDD8 pathway. EMBO Rep 9(3):280–286.  https://doi.org/10.1038/embor.2008.10 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Barbier-Torres L, Delgado TC, Garcia-Rodriguez JL, Zubiete-Franco I, Fernandez-Ramos D, Buque X, Cano A, Gutierrez-de Juan V, Fernandez-Dominguez I, Lopitz-Otsoa F, Fernandez-Tussy P, Boix L, Bruix J, Villa E, Castro A, Lu SC, Aspichueta P, Xirodimas D, Varela-Rey M, Mato JM, Beraza N, Martinez-Chantar ML (2015) Stabilization of LKB1 and Akt by neddylation regulates energy metabolism in liver cancer. Oncotarget 6(4):2509–2523.  https://doi.org/10.18632/oncotarget.3191 CrossRefPubMedGoogle Scholar
  17. 17.
    Li L, Wang M, Yu G, Chen P, Li H, Wei D, Zhu J, Xie L, Jia H, Shi J, Li C, Yao W, Wang Y, Gao Q, Jeong LS, Lee HW, Yu J, Hu F, Mei J, Wang P, Chu Y, Qi H, Yang M, Dong Z, Sun Y, Hoffman RM, Jia L (2014) Overactivated neddylation pathway as a therapeutic target in lung cancer. J Natl Cancer Inst 106(6):dju083.  https://doi.org/10.1093/jnci/dju083 CrossRefPubMedGoogle Scholar
  18. 18.
    Mori F, Nishie M, Piao YS, Kito K, Kamitani T, Takahashi H, Wakabayashi K (2005) Accumulation of NEDD8 in neuronal and glial inclusions of neurodegenerative disorders. Neuropathol Appl Neurobiol 31(1):53–61.  https://doi.org/10.1111/j.1365-2990.2004.00603.x CrossRefPubMedGoogle Scholar
  19. 19.
    Salon C, Brambilla E, Brambilla C, Lantuejoul S, Gazzeri S, Eymin B (2007) Altered pattern of Cul-1 protein expression and neddylation in human lung tumours: relationships with CAND1 and cyclin E protein levels. J Pathol 213(3):303–310.  https://doi.org/10.1002/path.2223 CrossRefPubMedGoogle Scholar
  20. 20.
    Zheng Q, Huang T, Zhang L, Zhou Y, Luo H, Xu H, Wang X (2016) Dysregulation of ubiquitin–proteasome system in neurodegenerative diseases. Front Aging Neurosci 8:303.  https://doi.org/10.3389/fnagi.2016.00303 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Lub S, Maes K, Menu E, De Bruyne E, Vanderkerken K, Van Valckenborgh E (2016) Novel strategies to target the ubiquitin proteasome system in multiple myeloma. Oncotarget 7(6):6521–6537.  https://doi.org/10.18632/oncotarget.6658 CrossRefPubMedGoogle Scholar
  22. 22.
    Kane RC, Bross PF, Farrell AT, Pazdur R (2003) Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy. Oncol 8(6):508–513Google Scholar
  23. 23.
    Hideshima T, Richardson P, Chauhan D, Palombella VJ, Elliott PJ, Adams J, Anderson KC (2001) The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res 61(7):3071–3076PubMedGoogle Scholar
  24. 24.
    Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, Demo SD, Bennett MK, van Leeuwen FW, Chanan-Khan AA, Orlowski RZ (2007) Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin–proteasome pathway, against preclinical models of multiple myeloma. Blood 110(9):3281–3290.  https://doi.org/10.1182/blood-2007-01-065888 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Feling RH, Buchanan GO, Mincer TJ, Kauffman CA, Jensen PR, Fenical W (2003) Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus salinospora. Angew Chem Int Ed Engl 42(3):355–357.  https://doi.org/10.1002/anie.200390115 CrossRefPubMedGoogle Scholar
  26. 26.
    Wu S, Yu L (2016) Targeting cullin-RING ligases for cancer treatment: rationales, advances and therapeutic implications. Cytotechnology 68(1):1–8.  https://doi.org/10.1007/s10616-015-9870-0 CrossRefPubMedGoogle Scholar
  27. 27.
    Nalepa G, Rolfe M, Harper JW (2006) Drug discovery in the ubiquitin–proteasome system. Nat Rev Drug Discov 5(7):596–613.  https://doi.org/10.1038/nrd2056 CrossRefPubMedGoogle Scholar
  28. 28.
    Hideshima T, Ikeda H, Chauhan D, Okawa Y, Raje N, Podar K, Mitsiades C, Munshi NC, Richardson PG, Carrasco RD, Anderson KC (2009) Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells. Blood 114(5):1046–1052.  https://doi.org/10.1182/blood-2009-01-199604 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Roccaro AM, Hideshima T, Raje N, Kumar S, Ishitsuka K, Yasui H, Shiraishi N, Ribatti D, Nico B, Vacca A, Dammacco F, Richardson PG, Anderson KC (2006) Bortezomib mediates antiangiogenesis in multiple myeloma via direct and indirect effects on endothelial cells. Cancer Res 66(1):184–191.  https://doi.org/10.1158/0008-5472.can-05-1195 CrossRefPubMedGoogle Scholar
  30. 30.
    Dorsey BD, Iqbal M, Chatterjee S, Menta E, Bernardini R, Bernareggi A, Cassara PG, D’Arasmo G, Ferretti E, De Munari S, Oliva A, Pezzoni G, Allievi C, Strepponi I, Ruggeri B, Ator MA, Williams M, Mallamo JP (2008) Discovery of a potent, selective, and orally active proteasome inhibitor for the treatment of cancer. J Med Chem 51(4):1068–1072.  https://doi.org/10.1021/jm7010589 CrossRefPubMedGoogle Scholar
  31. 31.
    Piva R, Ruggeri B, Williams M, Costa G, Tamagno I, Ferrero D, Giai V, Coscia M, Peola S, Massaia M, Pezzoni G, Allievi C, Pescalli N, Cassin M, di Giovine S, Nicoli P, de Feudis P, Strepponi I, Roato I, Ferracini R, Bussolati B, Camussi G, Jones-Bolin S, Hunter K, Zhao H, Neri A, Palumbo A, Berkers C, Ovaa H, Bernareggi A, Inghirami G (2008) CEP-18770: a novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood 111(5):2765–2775.  https://doi.org/10.1182/blood-2007-07-100651 CrossRefPubMedGoogle Scholar
  32. 32.
    Demo SD, Kirk CJ, Aujay MA, Buchholz TJ, Dajee M, Ho MN, Jiang J, Laidig GJ, Lewis ER, Parlati F, Shenk KD, Smyth MS, Sun CM, Vallone MK, Woo TM, Molineaux CJ, Bennett MK (2007) Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res 67(13):6383–6391.  https://doi.org/10.1158/0008-5472.can-06-4086 CrossRefPubMedGoogle Scholar
  33. 33.
    Allegra A, Alonci A, Gerace D, Russo S, Innao V, Calabro L, Musolino C (2014) New orally active proteasome inhibitors in multiple myeloma. Leuk Res 38(1):1–9.  https://doi.org/10.1016/j.leukres.2013.10.018 CrossRefPubMedGoogle Scholar
  34. 34.
    Kupperman E, Lee EC, Cao Y, Bannerman B, Fitzgerald M, Berger A, Yu J, Yang Y, Hales P, Bruzzese F, Liu J, Blank J, Garcia K, Tsu C, Dick L, Fleming P, Yu L, Manfredi M, Rolfe M, Bolen J (2010) Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res 70(5):1970–1980.  https://doi.org/10.1158/0008-5472.can-09-2766 CrossRefPubMedGoogle Scholar
  35. 35.
    Yang Y, Kitagaki J, Dai RM, Tsai YC, Lorick KL, Ludwig RL, Pierre SA, Jensen JP, Davydov IV, Oberoi P, Li CC, Kenten JH, Beutler JA, Vousden KH, Weissman AM (2007) Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics. Cancer Res 67(19):9472–9481.  https://doi.org/10.1158/0008-5472.can-07-0568 CrossRefPubMedGoogle Scholar
  36. 36.
    Ungermannova D, Parker SJ, Nasveschuk CG, Chapnick DA, Phillips AJ, Kuchta RD, Liu X (2012) Identification and mechanistic studies of a novel ubiquitin E1 inhibitor. J Biomol Screen 17(4):421–434.  https://doi.org/10.1177/1087057111433843 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Kitagaki J, Yang Y, Saavedra JE, Colburn NH, Keefer LK, Perantoni AO (2009) Nitric oxide prodrug JS-K inhibits ubiquitin E1 and kills tumor cells retaining wild-type p53. Oncogene 28(4):619–624.  https://doi.org/10.1038/onc.2008.401 CrossRefPubMedGoogle Scholar
  38. 38.
    Xu GW, Ali M, Wood TE, Wong D, Maclean N, Wang X, Gronda M, Skrtic M, Li X, Hurren R, Mao X, Venkatesan M, Beheshti Zavareh R, Ketela T, Reed JC, Rose D, Moffat J, Batey RA, Dhe-Paganon S, Schimmer AD (2010) The ubiquitin-activating enzyme E1 as a therapeutic target for the treatment of leukemia and multiple myeloma. Blood 115(11):2251–2259.  https://doi.org/10.1182/blood-2009-07-231191 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Gu Y, Kaufman JL, Bernal L, Torre C, Matulis SM, Harvey RD, Chen J, Sun SY, Boise LH, Lonial S (2014) MLN4924, an NAE inhibitor, suppresses AKT and mTOR signaling via upregulation of REDD1 in human myeloma cells. Blood 123(21):3269–3276.  https://doi.org/10.1182/blood-2013-08-521914 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Brownell JE, Sintchak MD, Gavin JM, Liao H, Bruzzese FJ, Bump NJ, Soucy TA, Milhollen MA, Yang X, Burkhardt AL, Ma J, Loke HK, Lingaraj T, Wu D, Hamman KB, Spelman JJ, Cullis CA, Langston SP, Vyskocil S, Sells TB, Mallender WD, Visiers I, Li P, Claiborne CF, Rolfe M, Bolen JB, Dick LR (2010) Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ. Mol Cell 37(1):102–111.  https://doi.org/10.1016/j.molcel.2009.12.024 CrossRefPubMedGoogle Scholar
  41. 41.
    Ceccarelli DF, Tang X, Pelletier B, Orlicky S, Xie W, Plantevin V, Neculai D, Chou YC, Ogunjimi A, Al-Hakim A, Varelas X, Koszela J, Wasney GA, Vedadi M, Dhe-Paganon S, Cox S, Xu S, Lopez-Girona A, Mercurio F, Wrana J, Durocher D, Meloche S, Webb DR, Tyers M, Sicheri F (2011) An allosteric inhibitor of the human Cdc34 ubiquitin-conjugating enzyme. Cell 145(7):1075–1087.  https://doi.org/10.1016/j.cell.2011.05.039 CrossRefPubMedGoogle Scholar
  42. 42.
    Issaeva N, Bozko P, Enge M, Protopopova M, Verhoef LG, Masucci M, Pramanik A, Selivanova G (2004) Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med 10(12):1321–1328.  https://doi.org/10.1038/nm1146 CrossRefPubMedGoogle Scholar
  43. 43.
    Gu D, Wang S, Kuiatse I, Wang H, He J, Dai Y, Jones RJ, Bjorklund CC, Yang J, Grant S, Orlowski RZ (2014) Inhibition of the MDM2 E3 Ligase induces apoptosis and autophagy in wild-type and mutant p53 models of multiple myeloma, and acts synergistically with ABT-737. PLoS One 9(9):e103015.  https://doi.org/10.1371/journal.pone.0103015 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Chargari C, Leteur C, Angevin E, Bashir T, Schoentjes B, Arts J, Janicot M, Bourhis J, Deutsch E (2011) Preclinical assessment of JNJ-26854165 (Serdemetan), a novel tryptamine compound with radiosensitizing activity in vitro and in tumor xenografts. Cancer Lett 312(2):209–218.  https://doi.org/10.1016/j.canlet.2011.08.011 CrossRefPubMedGoogle Scholar
  45. 45.
    Peterson LF, Sun H, Liu Y, Potu H, Kandarpa M, Ermann M, Courtney SM, Young M, Showalter HD, Sun D, Jakubowiak A, Malek SN, Talpaz M, Donato NJ (2015) Targeting deubiquitinase activity with a novel small-molecule inhibitor as therapy for B-cell malignancies. Blood 125(23):3588–3597.  https://doi.org/10.1182/blood-2014-10-605584 CrossRefPubMedGoogle Scholar
  46. 46.
    Chen HY, Chen RH (2016) Cullin 3 ubiquitin ligases in cancer biology: functions and therapeutic implications. Front Oncol 6:113.  https://doi.org/10.3389/fonc.2016.00113 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Sarikas A, Hartmann T, Pan ZQ (2011) The cullin protein family. Genome Biol 12(4):220.  https://doi.org/10.1186/gb-2011-12-4-220 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Lee J, Zhou P (2010) Cullins and cancer. Genes Cancer 1(7):690–699.  https://doi.org/10.1177/1947601910382899 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Pan ZQ, Kentsis A, Dias DC, Yamoah K, Wu K (2004) Nedd8 on cullin: building an expressway to protein destruction. Oncogene 23(11):1985–1997.  https://doi.org/10.1038/sj.onc.1207414 CrossRefPubMedGoogle Scholar
  50. 50.
    Duda DM, Borg LA, Scott DC, Hunt HW, Hammel M, Schulman BA (2008) Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation. Cell 134(6):995–1006.  https://doi.org/10.1016/j.cell.2008.07.022 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Zheng J, Yang X, Harrell JM, Ryzhikov S, Shim EH, Lykke-Andersen K, Wei N, Sun H, Kobayashi R, Zhang H (2002) CAND1 binds to unneddylated CUL1 and regulates the formation of SCF ubiquitin E3 ligase complex. Mol Cell 10(6):1519–1526CrossRefPubMedGoogle Scholar
  52. 52.
    Merlet J, Burger J, Gomes JE, Pintard L (2009) Regulation of cullin-RING E3 ubiquitin-ligases by neddylation and dimerization. Cell Mol Life Sci 66(11–12):1924–1938.  https://doi.org/10.1007/s00018-009-8712-7 CrossRefPubMedGoogle Scholar
  53. 53.
    Merlet J, Burger J, Gomes JE, Pintard L (2009) Regulation of cullin-RING E3 ubiquitin-ligases by neddylation and dimerization. Cell Mol Life Sci CMLS 66(11–12):1924–1938.  https://doi.org/10.1007/s00018-009-8712-7 CrossRefPubMedGoogle Scholar
  54. 54.
    Wimuttisuk W, Singer JD (2007) The Cullin3 ubiquitin ligase functions as a Nedd8-bound heterodimer. Mol Biol Cell 18(3):899–909.  https://doi.org/10.1091/mbc.E06-06-0542 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Soucy TA, Smith PG, Rolfe M (2009) Targeting NEDD8-activated cullin-RING ligases for the treatment of cancer. Clin Cancer Res 15(12):3912–3916.  https://doi.org/10.1158/1078-0432.CCR-09-0343 CrossRefPubMedGoogle Scholar
  56. 56.
    Watson IR, Blanch A, Lin DC, Ohh M, Irwin MS (2006) Mdm2-mediated NEDD8 modification of TAp73 regulates its transactivation function. J Biol Chem 281(45):34096–34103.  https://doi.org/10.1074/jbc.M603654200 CrossRefPubMedGoogle Scholar
  57. 57.
    Gao F, Cheng J, Shi T, Yeh ET (2006) Neddylation of a breast cancer-associated protein recruits a class III histone deacetylase that represses NFkappaB-dependent transcription. Nat Cell Biol 8(10):1171–1177.  https://doi.org/10.1038/ncb1483 CrossRefPubMedGoogle Scholar
  58. 58.
    Batinac T, Gruber F, Lipozencic J, Zamolo-Koncar G, Stasic A, Brajac I (2003) Protein p53—structure, function, and possible therapeutic implications. Acta Dermatovenerol Croat ADC 11(4):225–230PubMedGoogle Scholar
  59. 59.
    Harper JW (2004) Neddylating the guardian; Mdm2 catalyzed conjugation of Nedd8 to p53. Cell 118(1):2–4.  https://doi.org/10.1016/j.cell.2004.06.015 CrossRefPubMedGoogle Scholar
  60. 60.
    Abida WM, Nikolaev A, Zhao W, Zhang W, Gu W (2007) FBXO11 promotes the Neddylation of p53 and inhibits its transcriptional activity. J Biol Chem 282(3):1797–1804.  https://doi.org/10.1074/jbc.M609001200 CrossRefPubMedGoogle Scholar
  61. 61.
    Wang Z, Sun Y (2010) Targeting p53 for novel anticancer therapy. Transl Oncol 3(1):1–12CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Brooks CL, Gu W (2003) Ubiquitination, phosphorylation and acetylation: the molecular basis for p53 regulation. Curr Opin Cell Biol 15(2):164–171CrossRefPubMedGoogle Scholar
  63. 63.
    Nakamura S, Roth JA, Mukhopadhyay T (2000) Multiple lysine mutations in the C-terminal domain of p53 interfere with MDM2-dependent protein degradation and ubiquitination. Mol Cell Biol 20(24):9391–9398CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Nakagawa T, Takahashi M, Ozaki T, Watanabe Ki K, Todo S, Mizuguchi H, Hayakawa T, Nakagawara A (2002) Autoinhibitory regulation of p73 by Delta Np73 to modulate cell survival and death through a p73-specific target element within the Delta Np73 promoter. Mol Cell Biol 22(8):2575–2585CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Concin N, Becker K, Slade N, Erster S, Mueller-Holzner E, Ulmer H, Daxenbichler G, Zeimet A, Zeillinger R, Marth C, Moll UM (2004) Transdominant DeltaTAp73 isoforms are frequently up-regulated in ovarian cancer. Evidence for their role as epigenetic p53 inhibitors in vivo. Cancer Res 64(7):2449–2460CrossRefPubMedGoogle Scholar
  66. 66.
    Abdelmohsen K, Gorospe M (2010) Posttranscriptional regulation of cancer traits by HuR. Wiley Interdiscip Rev RNA 1(2):214–229.  https://doi.org/10.1002/wrna.4 CrossRefPubMedGoogle Scholar
  67. 67.
    Hardie DG, Alessi DR (2013) LKB1 and AMPK and the cancer-metabolism link—ten years after. BMC Biol 11:36.  https://doi.org/10.1186/1741-7007-11-36 CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Soucy TA, Smith PG, Milhollen MA, Berger AJ, Gavin JM, Adhikari S, Brownell JE, Burke KE, Cardin DP, Critchley S, Cullis CA, Doucette A, Garnsey JJ, Gaulin JL, Gershman RE, Lublinsky AR, McDonald A, Mizutani H, Narayanan U, Olhava EJ, Peluso S, Rezaei M, Sintchak MD, Talreja T, Thomas MP, Traore T, Vyskocil S, Weatherhead GS, Yu J, Zhang J, Dick LR, Claiborne CF, Rolfe M, Bolen JB, Langston SP (2009) An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 458(7239):732–736.  https://doi.org/10.1038/nature07884 CrossRefPubMedGoogle Scholar
  69. 69.
    Gong L, Yeh ET (1999) Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J Biol Chem 274(17):12036–12042CrossRefPubMedGoogle Scholar
  70. 70.
    Godbersen JC, Humphries LA, Danilova OV, Kebbekus PE, Brown JR, Eastman A, Danilov AV (2014) The Nedd8-activating enzyme inhibitor MLN4924 thwarts microenvironment-driven NF-kappaB activation and induces apoptosis in chronic lymphocytic leukemia B cells. Clin Cancer Res 20(6):1576–1589.  https://doi.org/10.1158/1078-0432.CCR-13-0987 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Han K, Wang Q, Cao H, Qiu G, Cao J, Li X, Wang J, Shen B, Zhang J (2016) The NEDD8-activating enzyme inhibitor MLN4924 induces G2 arrest and apoptosis in T-cell acute lymphoblastic leukemia. Oncotarget 7(17):23812–23824.  https://doi.org/10.18632/oncotarget.8068 PubMedPubMedCentralGoogle Scholar
  72. 72.
    Milhollen MA, Traore T, Adams-Duffy J, Thomas MP, Berger AJ, Dang L, Dick LR, Garnsey JJ, Koenig E, Langston SP, Manfredi M, Narayanan U, Rolfe M, Staudt LM, Soucy TA, Yu J, Zhang J, Bolen JB, Smith PG (2010) MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-κB-dependent lymphoma. Blood 116(9):1515–1523.  https://doi.org/10.1182/blood-2010-03-272567 CrossRefPubMedGoogle Scholar
  73. 73.
    Huang DT, Miller DW, Mathew R, Cassell R, Holton JM, Roussel MF, Schulman BA (2004) A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8. Nat Struct Mol Biol 11(10):927–935.  https://doi.org/10.1038/nsmb826 CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Amir RE, Iwai K, Ciechanover A (2002) The NEDD8 pathway is essential for SCF(beta-TrCP)-mediated ubiquitination and processing of the NF-kappa B precursor p105. J Biol Chem 277(26):23253–23259.  https://doi.org/10.1074/jbc.M200967200 CrossRefPubMedGoogle Scholar
  75. 75.
    Milhollen MA, Narayanan U, Soucy TA, Veiby PO, Smith PG, Amidon B (2011) Inhibition of NEDD8-activating enzyme induces rereplication and apoptosis in human tumor cells consistent with deregulating CDT1 turnover. Cancer Res 71(8):3042–3051.  https://doi.org/10.1158/0008-5472.CAN-10-2122 CrossRefPubMedGoogle Scholar
  76. 76.
    Lin JJ, Milhollen MA, Smith PG, Narayanan U, Dutta A (2010) NEDD8-targeting drug MLN4924 elicits DNA rereplication by stabilizing Cdt1 in S phase, triggering checkpoint activation, apoptosis, and senescence in cancer cells. Cancer Res 70(24):10310–10320.  https://doi.org/10.1158/0008-5472.CAN-10-2062 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Vaziri C, Saxena S, Jeon Y, Lee C, Murata K, Machida Y, Wagle N, Hwang DS, Dutta A (2003) A p53-dependent checkpoint pathway prevents rereplication. Mol Cell 11(4):997–1008CrossRefPubMedGoogle Scholar
  78. 78.
    Benamar M, Guessous F, Du K, Corbett P, Obeid J, Gioeli D, Slingluff CL Jr, Abbas T (2016) Inactivation of the CRL4-CDT2-SET8/p21 ubiquitylation and degradation axis underlies the therapeutic efficacy of pevonedistat in melanoma. EBioMedicine 10:85–100.  https://doi.org/10.1016/j.ebiom.2016.06.023 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Abbas T, Dutta A (2011) CRL4Cdt2: master coordinator of cell cycle progression and genome stability. Cell Cycle 10(2):241–249.  https://doi.org/10.4161/cc.10.2.14530 CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Tong S, Si Y, Yu H, Zhang L, Xie P, Jiang W (2017) MLN4924 (Pevonedistat), a protein neddylation inhibitor, suppresses proliferation and migration of human clear cell renal cell carcinoma. Sci Rep 7(1):5599.  https://doi.org/10.1038/s41598-017-06098-y CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    de Sousa GF, Lima Mde A, Custodio DF, Freitas VM, Monteiro G (2015) Chemogenomic study of carboplatin in Saccharomyces cerevisiae: inhibition of the neddylation process overcomes cellular resistance mediated by HuR and cullin proteins. PLoS One 10(12):e0145377.  https://doi.org/10.1371/journal.pone.0145377 CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Xu Q, Lin G, Xu H, Hu L, Wang Y, Du S, Deng W, Hu W, Cheng W, Jiang K (2018) MLN4924 neddylation inhibitor promotes cell death in paclitaxel-resistant human lung adenocarcinoma cells. Oncology Lett 15(1):515–521.  https://doi.org/10.3892/ol.2017.7314 Google Scholar
  83. 83.
    Bhatia S, Pavlick AC, Boasberg P, Thompson JA, Mulligan G, Pickard MD, Faessel H, Dezube BJ, Hamid O (2016) A phase I study of the investigational NEDD8-activating enzyme inhibitor pevonedistat (TAK-924/MLN4924) in patients with metastatic melanoma. Investig New Drugs 34(4):439–449.  https://doi.org/10.1007/s10637-016-0348-5 CrossRefGoogle Scholar
  84. 84.
    Reihe CA, Pekas N, Wu P, Wang X (2017) Systemic inhibition of neddylation by 3-day MLN4924 treatment regime does not impair autophagic flux in mouse hearts and brains. Am J Cardiovasc Dis 7(6):134–150PubMedPubMedCentralGoogle Scholar
  85. 85.
    Jin J, Cardozo T, Lovering RC, Elledge SJ, Pagano M, Harper JW (2004) Systematic analysis and nomenclature of mammalian F-box proteins. Genes Dev 18(21):2573–2580.  https://doi.org/10.1101/gad.1255304 CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Abbas T, Shibata E, Park J, Jha S, Karnani N, Dutta A (2010) CRL4(Cdt2) regulates cell proliferation and histone gene expression by targeting PR-Set7/Set8 for degradation. Mol Cell 40(1):9–21.  https://doi.org/10.1016/j.molcel.2010.09.014 CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Cukras S, Morffy N, Ohn T, Kee Y (2014) Inactivating UBE2M impacts the DNA damage response and genome integrity involving multiple cullin ligases. PLoS One 9(7):e101844.  https://doi.org/10.1371/journal.pone.0101844 CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Meyer-Schaller N, Chou YC, Sumara I, Martin DD, Kurz T, Katheder N, Hofmann K, Berthiaume LG, Sicheri F, Peter M (2009) The human Dcn1-like protein DCNL3 promotes Cul3 neddylation at membranes. Proc Natl Acad Sci USA 106(30):12365–12370.  https://doi.org/10.1073/pnas.0812528106 CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Keuss MJ, Thomas Y, McArthur R, Wood NT, Knebel A, Kurz T (2016) Characterization of the mammalian family of DCN-type NEDD8 E3 ligases. J Cell Sci 129(7):1441–1454.  https://doi.org/10.1242/jcs.181784 CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Cope GA, Deshaies RJ (2003) COP9 signalosome: a multifunctional regulator of SCF and other cullin-based ubiquitin ligases. Cell 114(6):663–671CrossRefPubMedGoogle Scholar
  91. 91.
    Bosu DR, Kipreos ET (2008) Cullin-RING ubiquitin ligases: global regulation and activation cycles. Cell Div 3:7.  https://doi.org/10.1186/1747-1028-3-7 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Clinical Research CenterXuyi People’s HospitalXuyiPeople’s Republic of China

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