Skip to main content
SpringerLink
Log in

Regulation of Stem Cells by Cullin-RING Ligase

  • Chapter
  • First Online:
Cullin-RING Ligases and Protein Neddylation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1217))

Abstract

Stem cells can remain quiescent, self-renewal, and differentiate into many types of cells and even cancer stem cells. The coordination of these complex processes maintains the homeostasis of the organism. Ubiquitination is an important posttranslational modification process that regulates protein stability and activity. The ubiquitination levels of stem cell-associated proteins are closely related with stem cell characteristics. Cullin-RING Ligases (CRLs) are the largest family of E3 ubiquitin ligases, accounting for approximately 20% of proteins degraded by proteasome. In this review, we discuss the role of CRLs in stem cell homeostasis, self-renewal, and differentiation and expound their ubiquitination substrates. In addition, we also discuss the effect of CRLs on the formation of cancer stem cells that may provide promising therapy strategies for cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ASB2:

Ankyrin-repeat SOCS box-containing protein 2

BTB:

Broad-Complex, tramtrack, and bric à brac

BTBD6A:

BTB/POZ domain-containing protein 6

CBs:

Cystoblasts

CCA:

Cholangiocarcinoma

CML:

Chronic myelogenous leukemia

COP1:

Constitutive photomorphogenic 1

CRBN:

Cereblon

CRLs:

Cullin-RING Ligases

CSCs:

Cancer stem cells

D4R:

Dopamine D4 receptor

DCAFs:

DDB1- and CUL4-associated factors

DCX:

DDB1-CUL4-X-box

DDB1:

DNA damage-binding protein 1

DLL1:

Delta-like ligand 1

Dpp:

Decapentaplegic

DSH:

Disheveled

ESCs:

Embryonic stem cells

FBW7:

F-box and WD repeat domain-containing protein 7

FLNA and FLNB:

Proteins filamin A and B

FWD1:

F-box and WD repeat-containing protein 1A

GSCs:

Germline stem cells

HECT:

Homologous to E6AP C-terminus

HIF1α:

Hypoxia-inducible factor α

HSCs:

Hematopoietic stem cells

iPSC:

Induced pluripotent stem cell

ISCs:

Intestinal stem cells

KBTBD8:

Kelch repeat and BTB domain-containing 8

KCTD2/10:

Potassium channel tetramerization domain-containing protein 2/10

KEAP1:

Kelch-like ECH-associated protein 1

KLHL12:

Kelch-like family member 12

LICs:

Leukemia-initiating cells

LRR:

Leucine-rich repeats

MaSCs:

Mammary stem cells

MB:

Medulloblastoma

MSCs:

Muscle stem cells

NF1:

Neurofibromatosis type 1

NPC:

Nasopharyngeal carcinoma

OSCs:

Osteoblast stem cells

OTUD7B:

OTU domain-containing protein 7B

PLZF:

Promyelocytic leukemia zinc finger

POZ:

Poxvirus and zinc finger

PrxIII:

Peroxiredoxin III

Ptc1:

Patched1

RA:

Retinoic acid

RBR:

Ring-in-between-Ring

RBX1:

Ring-box 1

RhoA:

Ras homolog family member A

RHOGEF:

RHO guanine nucleotide exchange factor

RING:

Really interesting new gene

ROS:

Reactive oxygen species

Shh:

Sonic hedgehog

SIMs:

Substrate-interacting motifs

Skp1:

S-phase kinase-associated protein 1

SOCS:

Suppressors of cytokine signaling

Sox2:

Sex-determining region Y-box 2

T-ALL:

T-cell acute lymphocytic leukemia

VHL:

Von Hippel-Lindau

References

  • Aberle H, Bauer A, Stappert J, Kispert A, Kemler R (1997) beta-catenin is a target for the ubiquitin-proteasome pathway. EMBO J 16:3797–3804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Akhoondi S, Sun D, von der Lehr N, Apostolidou S, Klotz K, Maljukova A, Cepeda D, Fiegl H, Dafou D, Marth C et al (2007) FBXW7/hCDC4 is a general tumor suppressor in human cancer. Cancer Res 67:9006–9012

    Article  CAS  PubMed  Google Scholar 

  • Ali A, Mistry BV, Ahmed HA, Abdulla R, Amer HA, Prince A, Alazami AM, Alkuraya FS, Assiri A (2018) Deletion of DDB1- and CUL4- associated factor-17 (Dcaf17) gene causes spermatogenesis defects and male infertility in mice. Sci Rep 8:9202

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Angers S, Thorpe CJ, Biechele TL, Goldenberg SJ, Zheng N, MacCoss MJ, Moon RT (2006) The KLHL12-Cullin-3 ubiquitin ligase negatively regulates the Wnt-beta-catenin pathway by targeting Dishevelled for degradation. Nat Cell Biol 8:348–357

    Article  CAS  PubMed  Google Scholar 

  • Ayyub C, Banerjee KK, Joti P (2015) Reduction of Cullin-2 in somatic cells disrupts differentiation of germline stem cells in the Drosophila ovary. Dev Biol 405:269–279

    Article  CAS  PubMed  Google Scholar 

  • Babaei-Jadidi R, Li N, Saadeddin A, Spencer-Dene B, Jandke A, Muhammad B, Ibrahim EE, Muraleedharan R, Abuzinadah M, Davis H et al (2011) FBXW7 influences murine intestinal homeostasis and cancer, targeting Notch, Jun, and DEK for degradation. J Exp Med 208:295–312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ballas N, Grunseich C, Lu DD, Speh JC, Mandel G (2005) REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis. Cell 121:645–657

    Article  CAS  PubMed  Google Scholar 

  • Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ et al (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449:1003–1007

    Article  CAS  PubMed  Google Scholar 

  • Becker AJ, Mc CE, Till JE (1963) Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197:452–454

    Article  CAS  PubMed  Google Scholar 

  • Bello NF, Lamsoul I, Heuze ML, Metais A, Moreaux G, Calderwood DA, Duprez D, Moog-Lutz C, Lutz PG (2009) The E3 ubiquitin ligase specificity subunit ASB2beta is a novel regulator of muscle differentiation that targets filamin B to proteasomal degradation. Cell Death Differ 16:921–932

    Article  CAS  PubMed  Google Scholar 

  • Betancur P, Bronner-Fraser M, Sauka-Spengler T (2010) Assembling neural crest regulatory circuits into a gene regulatory network. Annu Rev Cell Dev Biol 26:581–603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boix-Perales H, Horan I, Wise H, Lin HR, Chuang LC, Yew PR, Philpott A (2007) The E3 ubiquitin ligase skp2 regulates neural differentiation independent from the cell cycle. Neural Dev 2:27

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Buckley SM, Aranda-Orgilles B, Strikoudis A, Apostolou E, Loizou E, Moran-Crusio K, Farnsworth CL, Koller AA, Dasgupta R, Silva JC et al (2012) Regulation of pluripotency and cellular reprogramming by the ubiquitin-proteasome system. Cell Stem Cell 11:783–798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cai H, Liu A (2016) Spop promotes skeletal development and homeostasis by positively regulating Ihh signaling. Proc Natl Acad Sci U S A 113:14751–14756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Candi E, Rufini A, Terrinoni A, Dinsdale D, Ranalli M, Paradisi A, De Laurenzi V, Spagnoli LG, Catani MV, Ramadan S et al (2006) Differential roles of p63 isoforms in epidermal development: selective genetic complementation in p63 null mice. Cell Death Differ 13:1037–1047

    Article  CAS  PubMed  Google Scholar 

  • Cang Y, Zhang J, Nicholas SA, Bastien J, Li B, Zhou P, Goff SP (2006) Deletion of DDB1 in mouse brain and lens leads to p53-dependent elimination of proliferating cells. Cell 127:929–940

    Article  CAS  PubMed  Google Scholar 

  • Cardozo T, Pagano M (2004) The SCF ubiquitin ligase: insights into a molecular machine. Nat Rev Mol Cell Biol 5:739–751

    Article  CAS  PubMed  Google Scholar 

  • Chaharbakhshi E, Jemc JC (2016) Broad-complex, tramtrack, and bric-a-brac (BTB) proteins: Critical regulators of development. Genesis 54:505–518

    Article  CAS  PubMed  Google Scholar 

  • Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A (2003) Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113:643–655

    Article  CAS  PubMed  Google Scholar 

  • Chan CH, Li CF, Yang WL, Gao Y, Lee SW, Feng Z, Huang HY, Tsai KK, Flores LG, Shao Y et al (2012) The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, herceptin sensitivity, and tumorigenesis. Cell 149:1098–1111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chan CH, Morrow JK, Li CF, Gao Y, Jin G, Moten A, Stagg LJ, Ladbury JE, Cai Z, Xu D et al (2013) Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression. Cell 154:556–568

    Article  CAS  PubMed  Google Scholar 

  • Chen CL, Uthaya Kumar DB, Punj V, Xu J, Sher L, Tahara SM, Hess S, Machida K (2016) NANOG metabolically reprograms tumor-initiating stem-like cells through tumorigenic changes in oxidative phosphorylation and fatty acid metabolism. Cell Metab 23:206–219

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Yang Z, Meng M, Zhao Y, Dong N, Yan H, Liu L, Ding M, Peng HB, Shao F (2009) Cullin mediates degradation of RhoA through evolutionarily conserved BTB adaptors to control actin cytoskeleton structure and cell movement. Mol Cell 35:841–855

    Article  CAS  PubMed  Google Scholar 

  • Chen ZY, Wang X, Zhou Y, Offner G, Tseng CC (2005) Destabilization of Kruppel-like factor 4 protein in response to serum stimulation involves the ubiquitin-proteasome pathway. Cancer Res 65:10394–10400

    Article  CAS  PubMed  Google Scholar 

  • Cirak S, von Deimling F, Sachdev S, Errington WJ, Herrmann R, Bonnemann C, Brockmann K, Hinderlich S, Lindner TH, Steinbrecher A et al (2010) Kelch-like homologue 9 mutation is associated with an early onset autosomal dominant distal myopathy. Brain 133:2123–2135

    Article  PubMed  PubMed Central  Google Scholar 

  • Cleveland DW, Yamanaka K, Bomont P (2009) Gigaxonin controls vimentin organization through a tubulin chaperone-independent pathway. Hum Mol Genet 18:1384–1394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clevers H, Loh KM, Nusse R (2014) Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control. Science 346:1248012

    Article  PubMed  CAS  Google Scholar 

  • Cui CP, Zhang Y, Wang C, Yuan F, Li H, Yao Y, Chen Y, Li C, Wei W, Liu CH et al (2018) Dynamic ubiquitylation of Sox2 regulates proteostasis and governs neural progenitor cell differentiation. Nat Commun 9:4648

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • de Kretser DM, Loveland KL, Meinhardt A, Simorangkir D, Wreford N (1998) Spermatogenesis. Hum Reprod 13(Suppl 1):1–8

    Article  PubMed  Google Scholar 

  • Dixon J, Jones NC, Sandell LL, Jayasinghe SM, Crane J, Rey JP, Dixon MJ, Trainor PA (2006) Tcof1/Treacle is required for neural crest cell formation and proliferation deficiencies that cause craniofacial abnormalities. Proc Natl Acad Sci USA 103:13403–13408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donato V, Bonora M, Simoneschi D, Sartini D, Kudo Y, Saraf A, Florens L, Washburn MP, Stadtfeld M, Pinton P et al (2017) The TDH-GCN5L1-Fbxo15-KBP axis limits mitochondrial biogenesis in mouse embryonic stem cells. Nat Cell Biol 19:341–351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • du Puy L, Beqqali A, van Tol HT, Monshouwer-Kloots J, Passier R, Haagsman HP, Roelen BA (2012) Sarcosin (Krp1) in skeletal muscle differentiation: gene expression profiling and knockdown experiments. Int J Dev Biol 56:301–309

    Article  PubMed  CAS  Google Scholar 

  • Duan H, Wang Y, Aviram M, Swaroop M, Loo JA, Bian J, Tian Y, Mueller T, Bisgaier CL, Sun Y (1999) SAG, a novel zinc RING finger protein that protects cells from apoptosis induced by redox agents. Mol Cell Biol 19:3145–3155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duncan AW, Rattis FM, DiMascio LN, Congdon KL, Pazianos G, Zhao C, Yoon K, Cook JM, Willert K, Gaiano N et al (2005) Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol 6:314–322

    Article  CAS  PubMed  Google Scholar 

  • Ferguson JE 3rd, Wu Y, Smith K, Charles P, Powers K, Wang H, Patterson C (2007) ASB4 is a hydroxylation substrate of FIH and promotes vascular differentiation via an oxygen-dependent mechanism. Mol Cell Biol 27:6407–6419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferry C, Gaouar S, Fischer B, Boeglin M, Paul N, Samarut E, Piskunov A, Pankotai-Bodo G, Brino L, Rochette-Egly C (2011) Cullin 3 mediates SRC-3 ubiquitination and degradation to control the retinoic acid response. Proc Natl Acad Sci USA 108:20603–20608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I et al (2010) Selective inhibition of BET bromodomains. Nature 468:1067–1073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fischer ES, Bohm K, Lydeard JR, Yang H, Stadler MB, Cavadini S, Nagel J, Serluca F, Acker V, Lingaraju GM et al (2014) Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide. Nature 512:49–53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fuchs E, Chen T (2013) A matter of life and death: self-renewal in stem cells. EMBO Rep 14:39–48

    Article  CAS  PubMed  Google Scholar 

  • Galli F, Rossi M, D’Alessandra Y, De Simone M, Lopardo T, Haupt Y, Alsheich-Bartok O, Anzi S, Shaulian E, Calabro V et al (2010) MDM2 and Fbw7 cooperate to induce p63 protein degradation following DNA damage and cell differentiation. J Cell Sci 123:2423–2433

    Article  CAS  PubMed  Google Scholar 

  • Gao J, Buckley SM, Cimmino L, Guillamot M, Strikoudis A, Cang Y, Goff SP, Aifantis I (2015) The CUL4-DDB1 ubiquitin ligase complex controls adult and embryonic stem cell differentiation and homeostasis. Elife 4:e07539

    Article  PubMed  PubMed Central  Google Scholar 

  • Gerstein AV, Almeida TA, Zhao G, Chess E, Shih Ie M, Buhler K, Pienta K, Rubin MA, Vessella R, Papadopoulos N (2002) APC/CTNNB1 (beta-catenin) pathway alterations in human prostate cancers. Genes Chromosomes Cancer 34:9–16

    Article  CAS  PubMed  Google Scholar 

  • Gladwyn-Ng I, Huang L, Ngo L, Li SS, Qu Z, Vanyai HK, Cullen HD, Davis JM, Heng JI (2016) Bacurd1/Kctd13 and Bacurd2/Tnfaip1 are interacting partners to Rnd proteins which influence the long-term positioning and dendritic maturation of cerebral cortical neurons. Neural Dev 11:7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gladwyn-Ng IE, Li SS, Qu Z, Davis JM, Ngo L, Haas M, Singer J, Heng JI (2015) Bacurd2 is a novel interacting partner to Rnd2 which controls radial migration within the developing mammalian cerebral cortex. Neural Dev 10:9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gnarra JR, Tory K, Weng Y, Schmidt L, Wei MH, Li H, Latif F, Liu S, Chen F, Duh FM et al (1994) Mutations of the VHL tumour suppressor gene in renal carcinoma. Nat Genet 7:85–90

    Article  CAS  PubMed  Google Scholar 

  • Gonczy P (2008) Mechanisms of asymmetric cell division: flies and worms pave the way. Nat Rev Mol Cell Biol 9:355–366

    Article  PubMed  CAS  Google Scholar 

  • Gong W, Gohla RM, Bowlin KM, Koyano-Nakagawa N, Garry DJ, Shi X (2015) Kelch Repeat and BTB Domain Containing Protein 5 (Kbtbd5) Regulates Skeletal Muscle Myogenesis through the E2F1-DP1 Complex. J Biol Chem 290:15350–15361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Graham V, Khudyakov J, Ellis P, Pevny L (2003) SOX2 functions to maintain neural progenitor identity. Neuron 39:749–765

    Article  CAS  PubMed  Google Scholar 

  • Gupta VA, Beggs AH (2014) Kelch proteins: emerging roles in skeletal muscle development and diseases. Skelet Muscle 4:11

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Han T, Goralski M, Gaskill N, Capota E, Kim J, Ting TC, Xie Y, Williams NS, Nijhawan D (2017) Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science 356

    Google Scholar 

  • Hann SR, Eisenman RN (1984) Proteins encoded by the human c-myc oncogene: differential expression in neoplastic cells. Mol Cell Biol 4:2486–2497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hart M, Concordet JP, Lassot I, Albert I, del los Santos R, Durand H, Perret C, Rubinfeld B, Margottin F, Benarous R et al (1999) The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell. Curr Biol 9:207–210

    Article  CAS  PubMed  Google Scholar 

  • He S, Nakada D, Morrison SJ (2009) Mechanisms of stem cell self-renewal. Annu Rev Cell Dev Biol 25:377–406

    Article  CAS  PubMed  Google Scholar 

  • He YJ, McCall CM, Hu J, Zeng Y, Xiong Y (2006) DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. Genes Dev 20:2949–2954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heddleston JM, Li Z, Lathia JD, Bao S, Hjelmeland AB, Rich JN (2010) Hypoxia inducible factors in cancer stem cells. Br J Cancer 102:789–795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hernandez AR, Klein AM, Kirschner MW (2012) Kinetic responses of beta-catenin specify the sites of Wnt control. Science 338:1337–1340

    Article  CAS  PubMed  Google Scholar 

  • Heuze ML, Lamsoul I, Baldassarre M, Lad Y, Leveque S, Razinia Z, Moog-Lutz C, Calderwood DA, Lutz PG (2008) ASB2 targets filamins A and B to proteasomal degradation. Blood 112:5130–5140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hilton DJ, Richardson RT, Alexander WS, Viney EM, Willson TA, Sprigg NS, Starr R, Nicholson SE, Metcalf D, Nicola NA (1998) Twenty proteins containing a C-terminal SOCS box form five structural classes. Proc Natl Acad Sci U S A 95:114–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoeck JD, Jandke A, Blake SM, Nye E, Spencer-Dene B, Brandner S, Behrens A (2010) Fbw7 controls neural stem cell differentiation and progenitor apoptosis via Notch and c-Jun. Nat Neurosci 13:1365–1372

    Article  CAS  PubMed  Google Scholar 

  • Hong X, Liu W, Song R, Shah JJ, Feng X, Tsang CK, Morgan KM, Bunting SF, Inuzuka H, Zheng XF et al (2016) SOX9 is targeted for proteasomal degradation by the E3 ligase FBW7 in response to DNA damage. Nucl Acids Res 44:8855–8869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu D, Wan Y (2011) Regulation of Kruppel-like factor 4 by the anaphase promoting complex pathway is involved in TGF-beta signaling. J Biol Chem 286:6890–6901

    Article  CAS  PubMed  Google Scholar 

  • Huang X, Ordemann J, Muller JM, Dubiel W (2012) The COP9 signalosome, cullin 3 and Keap1 supercomplex regulates CHOP stability and adipogenesis. Biol Open 1:705–710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ilyas M, Tomlinson IP, Rowan A, Pignatelli M, Bodmer WF (1997) Beta-catenin mutations in cell lines established from human colorectal cancers. Proc Natl Acad Sci U S A 94:10330–10334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ito T, Ando H, Suzuki T, Ogura T, Hotta K, Imamura Y, Yamaguchi Y, Handa H (2010) Identification of a primary target of thalidomide teratogenicity. Science 327:1345–1350

    Article  CAS  PubMed  Google Scholar 

  • Jackson S, Xiong Y (2009) CRL4s: the CUL4-RING E3 ubiquitin ligases. Trends Biochem Sci 34:562–570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • James AW (2013) Review of signaling pathways governing MSC osteogenic and adipogenic differentiation. Scientifica (Cairo) 2013:684736

    Google Scholar 

  • Jiang J (2006) Regulation of Hh/Gli signaling by dual ubiquitin pathways. Cell Cycle 5:2457–2463

    Article  CAS  PubMed  Google Scholar 

  • Jiang J, Struhl G (1998) Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb. Nature 391:493–496

    Article  CAS  PubMed  Google Scholar 

  • Jin J, Cardozo T, Lovering RC, Elledge SJ, Pagano M, Harper JW (2004) Systematic analysis and nomenclature of mammalian F-box proteins. Genes Dev 18:2573–2580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin L, Pahuja KB, Wickliffe KE, Gorur A, Baumgartel C, Schekman R, Rape M (2012) Ubiquitin-dependent regulation of COPII coat size and function. Nature 482:495–500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kadaja M, Keyes BE, Lin M, Pasolli HA, Genander M, Polak L, Stokes N, Zheng D, Fuchs E (2014) SOX9: a stem cell transcriptional regulator of secreted niche signaling factors. Genes Dev 28:328–341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamura T, Maenaka K, Kotoshiba S, Matsumoto M, Kohda D, Conaway RC, Conaway JW, Nakayama KI (2004) VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases. Genes Dev 18:3055–3065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim EJ, Kim SH, Jin X, Jin X, Kim H (2017) KCTD2, an adaptor of Cullin3 E3 ubiquitin ligase, suppresses gliomagenesis by destabilizing c-Myc. Cell Death Differ 24:649–659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim MO, Kim SH, Cho YY, Nadas J, Jeong CH, Yao K, Kim DJ, Yu DH, Keum YS, Lee KY et al (2012) ERK1 and ERK2 regulate embryonic stem cell self-renewal through phosphorylation of Klf4. Nat Struct Mol Biol 19:283–290

    Article  CAS  PubMed  Google Scholar 

  • Kim SY, Herbst A, Tworkowski KA, Salghetti SE, Tansey WP (2003) Skp2 regulates Myc protein stability and activity. Mol Cell 11:1177–1188

    Article  CAS  PubMed  Google Scholar 

  • King B, Trimarchi T, Reavie L, Xu L, Mullenders J, Ntziachristos P, Aranda-Orgilles B, Perez-Garcia A, Shi J, Vakoc C et al (2013) The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability. Cell 153:1552–1566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kopanja D, Roy N, Stoyanova T, Hess RA, Bagchi S, Raychaudhuri P (2011) Cul4A is essential for spermatogenesis and male fertility. Dev Biol 352:278–287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kronke J, Udeshi ND, Narla A, Grauman P, Hurst SN, McConkey M, Svinkina T, Heckl D, Comer E, Li X et al (2014) Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science 343:301–305

    Article  PubMed  CAS  Google Scholar 

  • Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L et al (1993) Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 260:1317–1320

    Article  CAS  PubMed  Google Scholar 

  • Leblond CP, Walker BE (1956) Renewal of cell populations. Physiol Rev 36:255–276

    Article  CAS  PubMed  Google Scholar 

  • Lee DJ, Tseng HC, Wong SW, Wang Z, Deng M, Ko CC (2015) Dopaminergic effects on in vitro osteogenesis. Bone Res 3:15020

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee J, Zhou P (2007) DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase. Mol Cell 26:775–780

    Article  CAS  PubMed  Google Scholar 

  • Lee JW, Soung YH, Kim HJ, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ, Lee SH (2006) Mutational analysis of the hCDC4 gene in gastric carcinomas. Eur J Cancer 42:2369–2373

    Article  CAS  PubMed  Google Scholar 

  • Li C, Ao J, Fu J, Lee DF, Xu J, Lonard D, O’Malley BW (2011a) Tumor-suppressor role for the SPOP ubiquitin ligase in signal-dependent proteolysis of the oncogenic co-activator SRC-3/AIB1. Oncogene 30:4350–4364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Huang HY, Chen JG, Jiang L, Liu HL, Liu DG, Song TJ, He Q, Ma CG, Ma D et al (2006) Lactacystin inhibits 3T3-L1 adipocyte differentiation through induction of CHOP-10 expression. Biochem Biophys Res Commun 350:1–6

    Article  CAS  PubMed  Google Scholar 

  • Li X, Lu D, He F, Zhou H, Liu Q, Wang Y, Shao C, Gong Y (2011b) Cullin 4B protein ubiquitin ligase targets peroxiredoxin III for degradation. J Biol Chem 286:32344–32354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin CY, Chen CY, Yu CH, Yu IS, Lin SR, Wu JT, Lin YH, Kuo PL, Wu JC, Lin SW (2016) Human X-linked intellectual disability factor CUL4B Is required for post-meiotic sperm development and male fertility. Sci Rep 6:20227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin MY, Lin YM, Kao TC, Chuang HH, Chen RH (2011) PDZ-RhoGEF ubiquitination by Cullin3-KLHL20 controls neurotrophin-induced neurite outgrowth. J Cell Biol 193:985–994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Linossi EM, Nicholson SE (2012) The SOCS box-adapting proteins for ubiquitination and proteasomal degradation. IUBMB Life 64:316–323

    Article  CAS  PubMed  Google Scholar 

  • Liu L, Lee S, Zhang J, Peters SB, Hannah J, Zhang Y, Yin Y, Koff A, Ma L, Zhou P (2009) CUL4A abrogation augments DNA damage response and protection against skin carcinogenesis. Mol Cell 34:451–460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu TM, Lee EH, Lim B, Shyh-Chang N (2016) Concise review: balancing stem cell self-renewal and differentiation with PLZF. Stem Cells 34:277–287

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Hedvat CV, Mao S, Zhu XH, Yao J, Nguyen H, Koff A, Nimer SD (2006) The ETS protein MEF is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCFSkp2. Mol Cell Biol 26:3114–3123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu G, Middleton RE, Sun H, Naniong M, Ott CJ, Mitsiades CS, Wong KK, Bradner JE, Kaelin WG Jr (2014) The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science 343:305–309

    Article  CAS  PubMed  Google Scholar 

  • Majumder S (2006) REST in good times and bad: roles in tumor suppressor and oncogenic activities. Cell Cycle 5:1929–1935

    Article  CAS  PubMed  Google Scholar 

  • Malyukova A, Dohda T, von der Lehr N, Akhoondi S, Corcoran M, Heyman M, Spruck C, Grander D, Lendahl U, Sangfelt O (2007) The tumor suppressor gene hCDC4 is frequently mutated in human T-cell acute lymphoblastic leukemia with functional consequences for Notch signaling. Cancer Res 67:5611–5616

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto A, Onoyama I, Sunabori T, Kageyama R, Okano H, Nakayama KI (2011) Fbxw7-dependent degradation of Notch is required for control of “stemness” and neuronal-glial differentiation in neural stem cells. J Biol Chem 286:13754–13764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuoka S, Oike Y, Onoyama I, Iwama A, Arai F, Takubo K, Mashimo Y, Oguro H, Nitta E, Ito K et al (2008) Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL. Genes Dev 22:986–991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maugeri-Sacca M, Vigneri P, De Maria R (2011) Cancer stem cells and chemosensitivity. Clin Cancer Res 17:4942–4947

    Article  CAS  PubMed  Google Scholar 

  • Muerkoster S, Arlt A, Sipos B, Witt M, Grossmann M, Kloppel G, Kalthoff H, Folsch UR, Schafer H (2005) Increased expression of the E3-ubiquitin ligase receptor subunit betaTRCP1 relates to constitutive nuclear factor-kappaB activation and chemoresistance in pancreatic carcinoma cells. Cancer Res 65:1316–1324

    Article  PubMed  Google Scholar 

  • Nakayama K, Nagahama H, Minamishima YA, Matsumoto M, Nakamichi I, Kitagawa K, Shirane M, Tsunematsu R, Tsukiyama T, Ishida N et al (2000) Targeted disruption of Skp2 results in accumulation of cyclin E and p27(Kip1), polyploidy and centrosome overduplication. EMBO J 19:2069–2081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakayama K, Nagahama H, Minamishima YA, Miyake S, Ishida N, Hatakeyama S, Kitagawa M, Iemura S, Natsume T, Nakayama KI (2004) Skp2-mediated degradation of p27 regulates progression into mitosis. Dev Cell 6:661–672

    Article  CAS  PubMed  Google Scholar 

  • Nakayama KI, Nakayama K (2005) Regulation of the cell cycle by SCF-type ubiquitin ligases. Semin Cell Dev Biol 16:323–333

    Article  CAS  PubMed  Google Scholar 

  • Neumuller RA, Knoblich JA (2009) Dividing cellular asymmetry: asymmetric cell division and its implications for stem cells and cancer. Genes Dev 23:2675–2699

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nguyen LV, Vanner R, Dirks P, Eaves CJ (2012) Cancer stem cells: an evolving concept. Nat Rev Cancer 12:133–143

    Article  CAS  PubMed  Google Scholar 

  • Nie L, Perry SS, Zhao Y, Huang J, Kincade PW, Farrar MA, Sun XH (2008) Regulation of lymphocyte development by cell-type-specific interpretation of Notch signals. Mol Cell Biol 28:2078–2090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Neil J, Grim J, Strack P, Rao S, Tibbitts D, Winter C, Hardwick J, Welcker M, Meijerink JP, Pieters R et al (2007) FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors. J Exp Med 204:1813–1824

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Onoyama I, Tsunematsu R, Matsumoto A, Kimura T, de Alboran IM, Nakayama K, Nakayama KI (2007) Conditional inactivation of Fbxw7 impairs cell-cycle exit during T cell differentiation and results in lymphomatogenesis. J Exp Med 204:2875–2888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Onoyama I, Suzuki A, Matsumoto A, Tomita K, Katagiri H, Oike Y, Nakayama K, Nakayama KI (2011) Fbxw7 regulates lipid metabolism and cell fate decisions in the mouse liver. J Clin Invest 121:342–354

    Article  CAS  PubMed  Google Scholar 

  • Ooi L, Wood IC (2007) Chromatin crosstalk in development and disease: lessons from REST. Nat Rev Genet 8:544–554

    Article  CAS  PubMed  Google Scholar 

  • Passegue E, Wagers AJ (2006) Regulating quiescence: new insights into hematopoietic stem cell biology. Dev Cell 10:415–417

    Article  CAS  PubMed  Google Scholar 

  • Petroski MD, Deshaies RJ (2005) Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol 6:9–20

    Article  CAS  PubMed  Google Scholar 

  • Plechanovova A, Jaffray EG, Tatham MH, Naismith JH, Hay RT (2012) Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis. Nature 489:115–120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pozzebon ME, Varadaraj A, Mattoscio D, Jaffray EG, Miccolo C, Galimberti V, Tommasino M, Hay RT, Chiocca S (2013) BC-box protein domain-related mechanism for VHL protein degradation. Proc Natl Acad Sci U S A 110:18168–18173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rathinam C, Thien CB, Langdon WY, Gu H, Flavell RA (2008) The E3 ubiquitin ligase c-Cbl restricts development and functions of hematopoietic stem cells. Genes Dev 22:992–997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reavie L, Della Gatta G, Crusio K, Aranda-Orgilles B, Buckley SM, Thompson B, Lee E, Gao J, Bredemeyer AL, Helmink BA et al (2010) Regulation of hematopoietic stem cell differentiation by a single ubiquitin ligase-substrate complex. Nat Immunol 11:207–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reavie L, Buckley SM, Loizou E, Takeishi S, Aranda-Orgilles B, Ndiaye-Lobry D, Abdel-Wahab O, Ibrahim S, Nakayama KI, Aifantis I (2013) Regulation of c-Myc ubiquitination controls chronic myelogenous leukemia initiation and progression. Cancer Cell 23:362–375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reed SI (2003) Ratchets and clocks: the cell cycle, ubiquitylation and protein turnover. Nat Rev Mol Cell Biol 4:855–864

    Article  CAS  PubMed  Google Scholar 

  • Reiman JM, Knutson KL, Radisky DC (2010) Immune promotion of epithelial-mesenchymal transition and generation of breast cancer stem cells. Cancer Res 70:3005–3008

    Article  PubMed  PubMed Central  Google Scholar 

  • Ren K, Yuan J, Yang M, Gao X, Ding X, Zhou J, Hu X, Cao J, Deng X, Xiang S et al (2014) KCTD10 is involved in the cardiovascular system and Notch signaling during early embryonic development. PLoS One 9:e112275

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ridley AJ (2006) Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. Trends Cell Biol 16:522–529

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez S, Wang L, Mumaw C, Srour EF, Lo Celso C, Nakayama K, Carlesso N (2011) The SKP2 E3 ligase regulates basal homeostasis and stress-induced regeneration of HSCs. Blood 117:6509–6519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rowland BD, Bernards R (2006) Re-evaluating cell-cycle regulation by E2Fs. Cell 127:871–874

    Article  CAS  PubMed  Google Scholar 

  • Saha A, Lewis S, Kleiger G, Kuhlman B, Deshaies RJ (2011) Essential role for ubiquitin-ubiquitin-conjugating enzyme interaction in ubiquitin discharge from Cdc34 to substrate. Mol Cell 42:75–83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sambuughin N, Swietnicki W, Techtmann S, Matrosova V, Wallace T, Goldfarb L, Maynard E (2012) KBTBD13 interacts with Cullin 3 to form a functional ubiquitin ligase. Biochem Biophys Res Commun 421:743–749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simoes-Costa M, Bronner ME (2015) Establishing neural crest identity: a gene regulatory recipe. Development 142:242–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singer JD, Gurian-West M, Clurman B, Roberts JM (1999) Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells. Genes Dev 13:2375–2387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Skieterska K, Shen A, Clarisse D, Rondou P, Borroto-Escuela DO, Lintermans B, Fuxe K, Xiang YK, Van Craenenbroeck K (2016) Characterization of the interaction between the dopamine D4 receptor, KLHL12 and beta-arrestins. Cell Signal 28:1001–1014

    Article  CAS  PubMed  Google Scholar 

  • Sobieszczuk DF, Poliakov A, Xu Q, Wilkinson DG (2010) A feedback loop mediated by degradation of an inhibitor is required to initiate neuronal differentiation. Genes Dev 24:206–218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spruck CH, Won KA, Reed SI (1999) Deregulated cyclin E induces chromosome instability. Nature 401:297–300

    Article  CAS  PubMed  Google Scholar 

  • Staller P, Sulitkova J, Lisztwan J, Moch H, Oakeley EJ, Krek W (2003) Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL. Nature 425:307–311

    Article  CAS  PubMed  Google Scholar 

  • Stogios PJ, Downs GS, Jauhal JJ, Nandra SK, Prive GG (2005) Sequence and structural analysis of BTB domain proteins. Genome Biol 6:R82

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sumara I, Quadroni M, Frei C, Olma MH, Sumara G, Ricci R, Peter M (2007) A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells. Dev Cell 12:887–900

    Article  CAS  PubMed  Google Scholar 

  • Sun JK, Zhang B, Zhang J, Zhou JL (2007) Preparation of mouse KCTD10 antibody and expression analysis of KCTD10 in neuroepithelium of neural tube and dorsal root ganglion. Sheng Wu Gong Cheng Xue Bao 23:1011–1016

    Article  CAS  PubMed  Google Scholar 

  • Takebe N, Ivy SP (2010) Controversies in cancer stem cells: targeting embryonic signaling pathways. Clin Cancer Res 16:3106–3112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takebe N, Miele L, Harris PJ, Jeong W, Bando H, Kahn M, Yang SX, Ivy SP (2015) Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update. Nat Rev Clin Oncol 12:445–464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takeishi S, Nakayama KI (2014) Role of Fbxw7 in the maintenance of normal stem cells and cancer-initiating cells. Br J Cancer 111:1054–1059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takeishi S, Matsumoto A, Onoyama I, Naka K, Hirao A, Nakayama KI (2013) Ablation of Fbxw7 eliminates leukemia-initiating cells by preventing quiescence. Cancer Cell 23:347–361

    Article  CAS  PubMed  Google Scholar 

  • Takubo K, Goda N, Yamada W, Iriuchishima H, Ikeda E, Kubota Y, Shima H, Johnson RS, Hirao A, Suematsu M et al (2010) Regulation of the HIF-1alpha level is essential for hematopoietic stem cells. Cell Stem Cell 7:391–402

    Article  CAS  PubMed  Google Scholar 

  • Tan M, Zhao Y, Kim SJ, Liu M, Jia L, Saunders TL, Zhu Y, Sun Y (2011) SAG/RBX2/ROC2 E3 ubiquitin ligase is essential for vascular and neural development by targeting NF1 for degradation. Dev Cell 21:1062–1076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tetzlaff MT, Yu W, Li M, Zhang P, Finegold M, Mahon K, Harper JW, Schwartz RJ, Elledge SJ (2004) Defective cardiovascular development and elevated cyclin E and Notch proteins in mice lacking the Fbw7 F-box protein. Proc Natl Acad Sci U S A 101:3338–3345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson BJ, Jankovic V, Gao J, Buonamici S, Vest A, Lee JM, Zavadil J, Nimer SD, Aifantis I (2008) Control of hematopoietic stem cell quiescence by the E3 ubiquitin ligase Fbw7. J Exp Med 205:1395–1408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    Article  CAS  PubMed  Google Scholar 

  • Townley-Tilson WH, Wu Y, Ferguson JE 3rd, Patterson C (2014) The ubiquitin ligase ASB4 promotes trophoblast differentiation through the degradation of ID2. PLoS One 9:e89451

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Trumpp A, Essers M, Wilson A (2010) Awakening dormant haematopoietic stem cells. Nat Rev Immunol 10:201–209

    Article  CAS  PubMed  Google Scholar 

  • Ueda T, Nagamachi A, Takubo K, Yamasaki N, Matsui H, Kanai A, Nakata Y, Ikeda K, Konuma T, Oda H et al (2015) Fbxl10 overexpression in murine hematopoietic stem cells induces leukemia involving metabolic activation and upregulation of Nsg2. Blood 125:3437–3446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vernon AE, Devine C, Philpott A (2003) The cdk inhibitor p27Xic1 is required for differentiation of primary neurones in Xenopus. Development 130:85–92

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Huang Y, Guan Z, Zhang JL, Su HK, Zhang W, Yue CF, Yan M, Guan S, Liu QQ (2014a) E3-ligase Skp2 predicts poor prognosis and maintains cancer stem cell pool in nasopharyngeal carcinoma. Oncotarget 5:5591–5601

    PubMed  PubMed Central  Google Scholar 

  • Wang X, Jin J, Wan F, Zhao L, Chu H, Chen C, Liao G, Liu J, Yu Y, Teng H et al (2019) AMPK promotes SPOP-mediated NANOG degradation to regulate prostate cancer cell stemness. Dev Cell 48:345–360 e347

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Liu Y, Lu J, Zhang P, Wang Y, Xu Y, Wang Z, Mao JH, Wei G (2013) Rapamycin inhibits FBXW7 loss-induced epithelial-mesenchymal transition and cancer stem cell-like characteristics in colorectal cancer cells. Biochem Biophys Res Commun 434:352–356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Z, Liu P, Inuzuka H, Wei W (2014b) Roles of F-box proteins in cancer. Nat Rev Cancer 14:233–247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Warr MR, Pietras EM, Passegue E (2011) Mechanisms controlling hematopoietic stem cell functions during normal hematopoiesis and hematological malignancies. Wiley Interdiscip Rev Syst Biol Med 3:681–701

    Article  CAS  PubMed  Google Scholar 

  • Weissman AM (2001) Themes and variations on ubiquitylation. Nat Rev Mol Cell Biol 2:169–178

    Article  CAS  PubMed  Google Scholar 

  • Wenzel DM, Lissounov A, Brzovic PS, Klevit RE (2011) UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature 474:105–108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Westbrook TF, Hu G, Ang XL, Mulligan P, Pavlova NN, Liang A, Leng Y, Maehr R, Shi Y, Harper JW et al (2008) SCFbeta-TRCP controls oncogenic transformation and neural differentiation through REST degradation. Nature 452:370–374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie T, Spradling AC (1998) decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary. Cell 94:251–260

    Article  CAS  PubMed  Google Scholar 

  • Yada M, Hatakeyama S, Kamura T, Nishiyama M, Tsunematsu R, Imaki H, Ishida N, Okumura F, Nakayama K, Nakayama KI (2004) Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. The EMBO J 23:2116–2125

    Article  CAS  PubMed  Google Scholar 

  • Yamaki Y, Kagawa H, Hatta T, Natsume T, Kawahara H (2016) The C-terminal cytoplasmic tail of hedgehog receptor Patched1 is a platform for E3 ubiquitin ligase complexes. Mol Cell Biochem 414:1–12

    Article  CAS  PubMed  Google Scholar 

  • Yang H, Lu X, Liu Z, Chen L, Xu Y, Wang Y, Wei G, Chen Y (2015) FBXW7 suppresses epithelial-mesenchymal transition, stemness and metastatic potential of cholangiocarcinoma cells. Oncotarget 6:6310–6325

    PubMed  PubMed Central  Google Scholar 

  • Yau R, Rape M (2016) The increasing complexity of the ubiquitin code. Nat Cell Biol 18:579–586

    Article  CAS  PubMed  Google Scholar 

  • Yin Y, Lin C, Kim ST, Roig I, Chen H, Liu L, Veith GM, Jin RU, Keeney S, Jasin M et al (2011) The E3 ubiquitin ligase Cullin 4A regulates meiotic progression in mouse spermatogenesis. Dev Biol 356:51–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yin Y, Liu L, Yang C, Lin C, Veith GM, Wang C, Sutovsky P, Zhou P, Ma L (2016) Cell autonomous and nonautonomous function of CUL4B in mouse spermatogenesis. J Biol Chem 291:6923–6935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zebedee Z, Hara E (2001) Id proteins in cell cycle control and cellular senescence. Oncogene 20:8317–8325

    Article  CAS  PubMed  Google Scholar 

  • Zhao Y, Sun Y (2013) Cullin-RING Ligases as attractive anti-cancer targets. Curr Pharm Des 19:3215–3225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhuang M, Calabrese MF, Liu J, Waddell MB, Nourse A, Hammel M, Miller DJ, Walden H, Duda DM, Seyedin SN et al (2009) Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases. Mol Cell 36:39–50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Chronic Disease, Qingdao Municipal Hospital, Qingdao University, Qingdao, China

    Lin Fu

  2. State Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China

    Chun-Ping Cui & Lingqiang Zhang

Authors
  1. Lin Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chun-Ping Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lingqiang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lingqiang Zhang .

Editor information

Editors and Affiliations

  1. Radiation Oncology, University of Michigan, Ann Arbor, MI, USA

    Yi Sun

  2. Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Wenyi Wei

  3. Life Science Institute, Zhejiang University, Hangzhou, China

    Jianping Jin

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Fu, L., Cui, CP., Zhang, L. (2020). Regulation of Stem Cells by Cullin-RING Ligase. In: Sun, Y., Wei, W., Jin, J. (eds) Cullin-RING Ligases and Protein Neddylation. Advances in Experimental Medicine and Biology, vol 1217. Springer, Singapore. https://doi.org/10.1007/978-981-15-1025-0_6

Download citation

Publish with us

Policies and ethics

Search

Navigation