Home LiteratureArticle Details
PMID: 19775879 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Control of cell growth by the SCF and APC/C ubiquitin ligases.

Current opinion in cell biology ·Vol. 21 ·No. 6 ·2009-12-00 ·Pages 816-24

Skaar JR, Pagano M

Abstract

The ubiquitin-proteasome system plays key roles in the control of cell growth. The cell cycle, in particular, is highly regulated by the functions of the SCF and APC/C ubiquitin ligases, and perturbation of their function can result in tumorigenesis. Although the SCF and APC/C complexes are well established in growth control pathways, many aspects of their function remain unknown. Recent studies have shed light on the mechanism of SCF-mediated ubiquitination and new functions for the SCF complex and APC/C. Our expanding understanding of the roles of the SCF and APC/C complexes highlight the potential for targeted molecular therapies.

MeSH Terms
Animals Cell Cycle/physiology Cell Cycle Proteins/genetics,metabolism Cullin Proteins Humans Models, Biological Proteasome Endopeptidase Complex/genetics,metabolism SKP Cullin F-Box Protein Ligases/genetics,metabolism Signal Transduction Ubiquitin/genetics,metabolism Ubiquitin C/genetics,metabolism Ubiquitin-Protein Ligases/genetics,metabolism
Chemicals
Cell Cycle Proteins Cullin Proteins Ubiquitin Ubiquitin C SKP Cullin F-Box Protein Ligases Ubiquitin-Protein Ligases Proteasome Endopeptidase Complex
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Skaar Jeffrey R
Department of Pathology, NYU Cancer Institute, New York University School of Medicine, New York, NY 10016, USA.
Pagano Michele
References (73)
73 references, click to expand
  1. The COP9 signalosome: more than a protease.
    Trends Biochem Sci. 2008 Dec;33(12):592-600 PMID: 18926707
  2. betaTrCP- and Rsk1/2-mediated degradation of BimEL inhibits apoptosis.
    Mol Cell. 2009 Jan 16;33(1):109-16 PMID: 19150432
  3. Polyubiquitin chains: polymeric protein signals.
    Curr Opin Chem Biol. 2004 Dec;8(6):610-6 PMID: 15556404
  4. NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases.
    Mol Cell. 2002 Dec;10(6):1511-8 PMID: 12504025
  5. APC/C- and Mad2-mediated degradation of Cdc20 during spindle checkpoint activation.
    Cell Cycle. 2009 Jan 1;8(1):167-71 PMID: 19098431
  6. Quantitative analysis of in vitro ubiquitinated cyclin B1 reveals complex chain topology.
    Nat Cell Biol. 2006 Jul;8(7):700-10 PMID: 16799550
  7. The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint.
    Cell. 2008 Jul 25;134(2):256-67 PMID: 18662541
  8. Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery.
    Nature. 2008 Sep 4;455(7209):119-23 PMID: 18615013
  9. Control of chromosome stability by the beta-TrCP-REST-Mad2 axis.
    Nature. 2008 Mar 20;452(7185):365-9 PMID: 18354482
  10. The function of APC/CCdh1 in cell cycle and beyond.
    Cell Div. 2009 Jan 19;4:2 PMID: 19152694
  11. Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL.
    Genes Dev. 2008 Apr 15;22(8):986-91 PMID: 18367647
  12. Spindle checkpoint regulates Cdc20p stability in Saccharomyces cerevisiae.
    Genes Dev. 2004 Jun 15;18(12):1439-51 PMID: 15198982
  13. The CUL1 C-terminal sequence and ROC1 are required for efficient nuclear accumulation, NEDD8 modification, and ubiquitin ligase activity of CUL1.
    Mol Cell Biol. 2000 Nov;20(21):8185-97 PMID: 11027288
  14. Identification of SCF ubiquitin ligase substrates by global protein stability profiling.
    Science. 2008 Nov 7;322(5903):923-9 PMID: 18988848
  15. S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth.
    Science. 2006 Oct 20;314(5798):467-71 PMID: 17053147
  16. E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification.
    Mol Cell. 2009 Feb 27;33(4):483-95 PMID: 19250909
  17. Polo-like kinase-1 controls proteasome-dependent degradation of Claspin during checkpoint recovery.
    Curr Biol. 2006 Oct 10;16(19):1950-5 PMID: 16934469
  18. Ubiquitin ligases: cell-cycle control and cancer.
    Nat Rev Cancer. 2006 May;6(5):369-81 PMID: 16633365
  19. 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. 2004 Mar 9;101(10):3338-45 PMID: 14766969
  20. The SCF ubiquitin ligase: insights into a molecular machine.
    Nat Rev Mol Cell Biol. 2004 Sep;5(9):739-51 PMID: 15340381
  21. Destruction of Claspin by SCFbetaTrCP restrains Chk1 activation and facilitates recovery from genotoxic stress.
    Mol Cell. 2006 Aug 4;23(3):307-18 PMID: 16885021
  22. A novel mechanism by which thiazolidinediones facilitate the proteasomal degradation of cyclin D1 in cancer cells.
    J Biol Chem. 2008 Sep 26;283(39):26759-70 PMID: 18650423
  23. Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases.
    Cell. 2004 Nov 12;119(4):517-28 PMID: 15537541
  24. Modification of cullin-1 by ubiquitin-like protein Nedd8 enhances the activity of SCF(skp2) toward p27(kip1).
    Biochem Biophys Res Commun. 2000 Apr 21;270(3):1093-6 PMID: 10772955
  25. Conditional inactivation of Fbxw7 impairs cell-cycle exit during T cell differentiation and results in lymphomatogenesis.
    J Exp Med. 2007 Nov 26;204(12):2875-88 PMID: 17984302
  26. Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase.
    Dev Cell. 2003 Jun;4(6):813-26 PMID: 12791267
  27. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer.
    Nature. 2009 Apr 9;458(7239):732-6 PMID: 19360080
  28. Genomic stability and tumour suppression by the APC/C cofactor Cdh1.
    Nat Cell Biol. 2008 Jul;10(7):802-11 PMID: 18552834
  29. A Nedd8 conjugation pathway is essential for proteolytic targeting of p27Kip1 by ubiquitination.
    Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4579-84 PMID: 10781063
  30. Function and regulation of protein neddylation. 'Protein modifications: beyond the usual suspects' review series.
    EMBO Rep. 2008 Oct;9(10):969-76 PMID: 18802447
  31. Bora and the kinase Aurora a cooperatively activate the kinase Plk1 and control mitotic entry.
    Science. 2008 Jun 20;320(5883):1655-8 PMID: 18566290
  32. Cdc20: a WD40 activator for a cell cycle degradation machine.
    Mol Cell. 2007 Jul 6;27(1):3-16 PMID: 17612486
  33. FBXW7/hCDC4 is a general tumor suppressor in human cancer.
    Cancer Res. 2007 Oct 1;67(19):9006-12 PMID: 17909001
  34. Control of hematopoietic stem cell quiescence by the E3 ubiquitin ligase Fbw7.
    J Exp Med. 2008 Jun 9;205(6):1395-408 PMID: 18474632
  35. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex.
    Cell. 2008 May 16;133(4):653-65 PMID: 18485873
  36. Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex.
    Nature. 2002 Apr 18;416(6882):703-9 PMID: 11961546
  37. FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation.
    Nat Rev Cancer. 2008 Feb;8(2):83-93 PMID: 18094723
  38. Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21(CIP1/WAF1) and cyclin D proteins.
    Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11324-9 PMID: 9736735
  39. Preferential interaction of TIP120A with Cul1 that is not modified by NEDD8 and not associated with Skp1.
    Biochem Biophys Res Commun. 2003 Apr 18;303(4):1209-16 PMID: 12684064
  40. Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation.
    Mol Cell. 2008 Oct 10;32(1):21-31 PMID: 18851830
  41. SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase.
    Genes Dev. 2003 Dec 15;17(24):3062-74 PMID: 14681206
  42. SCFbetaTrCP-mediated degradation of Claspin regulates recovery from the DNA replication checkpoint response.
    Mol Cell. 2006 Aug 4;23(3):319-29 PMID: 16885022
  43. Plk1- and beta-TrCP-dependent degradation of Bora controls mitotic progression.
    J Cell Biol. 2008 Apr 7;181(1):65-78 PMID: 18378770
  44. Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo.
    Dev Cell. 2003 Jun;4(6):799-812 PMID: 12791266
  45. The anaphase-promoting complex/cyclosome: APC/C.
    J Cell Sci. 2006 Jun 15;119(Pt 12):2401-4 PMID: 16763193
  46. Conjugation of Nedd8 to CUL1 enhances the ability of the ROC1-CUL1 complex to promote ubiquitin polymerization.
    J Biol Chem. 2000 Oct 13;275(41):32317-24 PMID: 10921923
  47. The APC/C maintains the spindle assembly checkpoint by targeting Cdc20 for destruction.
    Nat Cell Biol. 2008 Dec;10(12):1411-20 PMID: 18997788
  48. M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP.
    Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4419-24 PMID: 15070733
  49. Global protein stability profiling in mammalian cells.
    Science. 2008 Nov 7;322(5903):918-23 PMID: 18988847
  50. The anaphase promoting complex/cyclosome: a machine designed to destroy.
    Nat Rev Mol Cell Biol. 2006 Sep;7(9):644-56 PMID: 16896351
  51. Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development.
    J Biol Chem. 2004 Mar 5;279(10):9417-23 PMID: 14672936
  52. The ubiquitin-proteasome pathway and pathogenesis of human diseases.
    Annu Rev Med. 1999;50:57-74 PMID: 10073263
  53. Nedd8 on cullin: building an expressway to protein destruction.
    Oncogene. 2004 Mar 15;23(11):1985-97 PMID: 15021886
  54. PARC and CUL7 form atypical cullin RING ligase complexes.
    Cancer Res. 2007 Mar 1;67(5):2006-14 PMID: 17332328
  55. The adaptor protein of the anaphase promoting complex Cdh1 is essential in maintaining replicative lifespan and in learning and memory.
    Nat Cell Biol. 2008 Sep;10(9):1083-9 PMID: 19160489
  56. Arabidopsis ETA2, an apparent ortholog of the human cullin-interacting protein CAND1, is required for auxin responses mediated by the SCF(TIR1) ubiquitin ligase.
    Plant Cell. 2004 Jul;16(7):1883-97 PMID: 15208392
  57. VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases.
    Genes Dev. 2004 Dec 15;18(24):3055-65 PMID: 15601820
  58. Themes and variations on ubiquitylation.
    Nat Rev Mol Cell Biol. 2001 Mar;2(3):169-78 PMID: 11265246
  59. Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer.
    Nat Rev Cancer. 2008 Jun;8(6):438-49 PMID: 18500245
  60. A critical role for FBXW8 and MAPK in cyclin D1 degradation and cancer cell proliferation.
    PLoS One. 2006 Dec 27;1:e128 PMID: 17205132
  61. Nedd8 modification of cul-1 activates SCF(beta(TrCP))-dependent ubiquitination of IkappaBalpha.
    Mol Cell Biol. 2000 Apr;20(7):2326-33 PMID: 10713156
  62. CAND1 binds to unneddylated CUL1 and regulates the formation of SCF ubiquitin E3 ligase complex.
    Mol Cell. 2002 Dec;10(6):1519-26 PMID: 12504026
  63. Function and regulation of cullin-RING ubiquitin ligases.
    Nat Rev Mol Cell Biol. 2005 Jan;6(1):9-20 PMID: 15688063
  64. Activation of Cdh1-dependent APC is required for G1 cell cycle arrest and DNA damage-induced G2 checkpoint in vertebrate cells.
    EMBO J. 2001 Nov 15;20(22):6499-508 PMID: 11707420
  65. Interwoven ubiquitination oscillators and control of cell cycle transitions.
    Sci STKE. 2004 Jul 13;2004(242):pe31 PMID: 15266102
  66. F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage.
    Nature. 2009 Jun 4;459(7247):722-5 PMID: 19412162
  67. Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation.
    Cell. 2008 Sep 19;134(6):995-1006 PMID: 18805092
  68. NEDD8 recruits E2-ubiquitin to SCF E3 ligase.
    EMBO J. 2001 Aug 1;20(15):4003-12 PMID: 11483504
  69. The ubiquitin system.
    Annu Rev Biochem. 1998;67:425-79 PMID: 9759494
  70. Systematic analysis and nomenclature of mammalian F-box proteins.
    Genes Dev. 2004 Nov 1;18(21):2573-80 PMID: 15520277
  71. The spindle-assembly checkpoint in space and time.
    Nat Rev Mol Cell Biol. 2007 May;8(5):379-93 PMID: 17426725
  72. Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex.
    Mol Cell. 2006 Nov 3;24(3):355-66 PMID: 17081987
  73. Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage.
    Nature. 2003 Nov 6;426(6962):87-91 PMID: 14603323
Article Info
Journal
Current opinion in cell biology
Abbr.
Curr Opin Cell Biol
ISSN
1879-0410
DOI
10.1016/j.ceb.2009.08.004
Published
2009-12-00
Epub
2009-00-21
Pages
816-24
Language
English
Region
England
NLM ID
8913428
PMCID
PMC2805079
Subset
IM
Grants
NCI NIH HHS · R21 CA125173-02 · United States
NIGMS NIH HHS · R01 GM057587 · United States
NCI NIH HHS · R21 CA125173 · United States
NCI NIH HHS · R37 CA076584-12 · United States
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · R01-GM057587 · United States
NCI NIH HHS · R37 CA076584 · United States
NCI NIH HHS · R37-CA076584 · United States
NIGMS NIH HHS · R01 GM057587-12 · United States
NCI NIH HHS · R21-CA125173 · United States
External Links
PubMed source DOI: 10.1016/j.ceb.2009.08.004 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2