Skip to main content
SpringerLink
Log in
Book cover

Conjugation and Deconjugation of Ubiquitin Family Modifiers pp 107–115Cite as

Assembly of K11-Linked Ubiquitin Chains by the Anaphase-Promoting Complex

  • Chapter

Part of the book series: Subcellular Biochemistry ((SCBI,volume 54))

Abstract

Ubiquitin chains are assembled, when a ubiquitin is connected to one of the seven Lys residues or the amino-terminus of a ubiquitin molecule already attached to a substrate. K48-linked ubiquitin chains target proteins for degradation by the 26S proteasome, while those chains connected through K63 regulate intracellular signaling cascades independently of protein degradation. Although all other linkages are detected in cells, their function is not well understood. Here, we review recent progress in delineating substrates, enzymes and functions of K11-linked ubiquitin chains. In particular, we discuss the mechanism of assembly for K11-linked chains by the human anaphase-promoting complex and its physiological E2s UbcH10 and Ube2S and we speculate on the particularities of these noncanonical chains in cells.

This is a preview of subscription content, 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 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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kerscher O, Felberbaum R, Hochstrasser M. Modification of proteins by ubiquitin and ubiquitin-like proteins. Annu Rev Cell Dev Biol 2006 22:159–80.

    Article  CAS  PubMed  Google Scholar 

  2. Mukhopadhyay D, Riezman H. Proteasome-independent functions of ubiquitin in endocytosis and signaling. Science 2007; 315:201–5.

    Article  CAS  PubMed  Google Scholar 

  3. Hochstrasser M. Lingering mysteries of ubiquitin-chain assembly. Cell 2006; 124:27–34.

    Article  PubMed  Google Scholar 

  4. Bennett EJ, Shaler TA, Woodman B et al. Global changes to the ubiquitin system in Huntigton’s disease. 2007; 448:704–8.

    CAS  Google Scholar 

  5. Xu P, Duong DM, Seyfried NT et al. Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell 2009; 137:133–45.

    Article  CAS  PubMed  Google Scholar 

  6. Spence J, Sadis S, Haas AL et al. A ubiquitin mutant with specific defects in DNA repair and multiubiquitination. Mol Cell Biol 1995; 15:1265–73.

    CAS  PubMed  Google Scholar 

  7. Grabbe C, Dikic I. Functional roles of ubiquitin-like domain (ULD) and ubiquitin-binding domain (UBD) containing proteins. Chem Rev 2009; 109:1481–94.

    Article  CAS  PubMed  Google Scholar 

  8. Chen ZJ, Sun LJ. Nonproteolytic functions of ubiquitin in cell signaling. Mol Cell 2009; 33:275–86.

    Article  CAS  PubMed  Google Scholar 

  9. Baboshina OV, Haas AL. Novel multiubiquitin chain linkages catalyzed by the conjugating enzymes E2EPF and RAD6 are recognized by 26 S proteasome subunit 5. J Biol Chem 1996; 271:2823–31.

    Article  CAS  PubMed  Google Scholar 

  10. Nishikawa H, Ooka S, Sato K et al. Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase. J Biol Chem 2004; 279:3916–24.

    Article  CAS  PubMed  Google Scholar 

  11. Jin L, Williamson A, Banerjee S et al. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell 2008; 133:653–65.

    Article  CAS  PubMed  Google Scholar 

  12. Tokunaga F, Sakata S, Saeki Y et al. Involvement of linear polyubiquitylation of NEMO in NFkappa-B activation. Nat Cell Biol 2009; 11:123–32.

    Article  CAS  PubMed  Google Scholar 

  13. Rahighi S, Ikeda F, Kawasaki M et al. Specific recognition of linear ubiquitin chains by NEMO is important for NFkappa-B activation. Cell 2009; 136:1098–109.

    Article  CAS  PubMed  Google Scholar 

  14. Peng J, Schwartz D, Elias JE et al. A proteomics approach to understanding protein ubiquitination. Nat Biotechnol 2003; 21:921–6.

    Article  CAS  PubMed  Google Scholar 

  15. Williamson et al. Identification of a physiological E2 module for the human Anaphase-Promoting Complex. PNAS 2009; under revision.

    Google Scholar 

  16. Richly H, Rape M, Braun S et al. A series of ubiquitin binding factors connects CDC48/p97 to substrate multiubiquitylation and proteasomal targeting. Cell 2005; 120:73–84.

    Article  CAS  PubMed  Google Scholar 

  17. Alexandru G, Graumann J, Smith GT et al. UBXD7 binds multiple ubiquitin ligases and implicates p97 in HIF1alpha turnover. Cell 2008; 134:804–16.

    Article  CAS  PubMed  Google Scholar 

  18. Peters JM. The anaphase-promoting complex/cyclosome: a machine designed to destroy. Nat Rev Mol Cell Biol 2006; 7:644–56.

    Article  CAS  PubMed  Google Scholar 

  19. King RW, Peters JM, Tugendreich S et al. A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. Cell 1995; 81:279–88.

    Article  CAS  PubMed  Google Scholar 

  20. Rape M, Reddy SK, Kirschner MW. The processivity of multiubiquitination by the APC determines the order of substrate degradation. Cell 2006; 124:89–103.

    Article  CAS  PubMed  Google Scholar 

  21. Reddy SK, Rape M, Kirschner MW. Ubiquitination by the anaphase-promoting complex drives spindle checkpoint inactivation. Nature 2007; 446:921–5.

    Article  CAS  PubMed  Google Scholar 

  22. Stegmeier F, Rape M, Draviam VM et al. Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities. Nature 2007; 446:876–81.

    Article  CAS  PubMed  Google Scholar 

  23. Goshima G, Wollmann R, Goodwin SS et al. Genes required for mitotic spindle assembly in Drosophila S2 cells. Science 2007; 316:417–21.

    Article  CAS  PubMed  Google Scholar 

  24. Margottin-Goguet F, Hsu JY, Loktev A et al. Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase. Dev Cell 2003; 4:813–26.

    Article  CAS  PubMed  Google Scholar 

  25. Yu H, King RW, Peters JM et al. Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation. Curr Biol 1996; 6:455–66.

    Article  CAS  PubMed  Google Scholar 

  26. Rodrigo-Brenni MC, Morgan DO. Sequential E2s drive polyubiquitin chain assembly on APC targets. Cell 2007; 130:127–39.

    Article  CAS  PubMed  Google Scholar 

  27. Michelle C, Vourc’h P, Mignon L et al. What was the set of ubiquitin and ubiquitin-like conjugating enzymes in the eukaryote common ancestor? J Mol Evol 2009; 68:616–28.

    Article  CAS  PubMed  Google Scholar 

  28. Máthé E, Kraft C, Giet R et al. The E2-C vihar is required for the correct spatiotemporal proteolysis of cyclin B and itself undergoes cyclical degradation. Curr Biol 2004; 14:1723–33.

    Article  PubMed  CAS  Google Scholar 

  29. Rape M, Kirschner MW. Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry. Nature 2004; 432:588–95.

    Article  CAS  PubMed  Google Scholar 

  30. Summers MK, Pan B, Mukhyala K et al. The unique N terminus of the UbcH10 E2 enzyme controls the threshold for APC activation and enhances checkpoint regulation of the APC. Mol Cell 2008; 31:544–56.

    Article  CAS  PubMed  Google Scholar 

  31. Wagner KW, Sapinoso LM, El-Rifai W et al. Overexpression, genomic amplification and therapeutic potential of inhibiting the UbcH10 ubiquitin conjugase in human carcinomas of diverse anatomic origin. Oncogene 2004; 23:6621–9.

    Article  CAS  PubMed  Google Scholar 

  32. Berlingieri MT, Pallante P, Guida M et al. UbcH10 expression may be a useful tool in the prognosis of ovarian carcinomas. Oncogene 2007; 26:2136–40.

    Article  CAS  PubMed  Google Scholar 

  33. Fujita T, Ikeda H, Kawasaki K et al. Clinicopathological relevance of UbcH10 in breast cancer. Cancer Sci. doi: 10.1111/j.1349-7006.2008.01026.

    Google Scholar 

  34. Pfleger CM, Kirschner MW. The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1. Genes Dev 2000; 14:655–65.

    CAS  PubMed  Google Scholar 

  35. Kirkpatrick DS, Hathaway NA, Hanna J et al. Quantitative analysis of in vitro ubiquitinated cyclin B1 reveals complex chain topology. Nature Cell Biol 2006; 8:700–10.

    Article  CAS  PubMed  Google Scholar 

  36. Ye Y, Rape M. Building a chain: E2 enzymes at work. Nat Rev Mol Cell Biol. in press.

    Google Scholar 

  37. Wirth KG, Ricci R, Giménez-Abián JF et al. Loss of the anaphase-promoting complex in quiescent cells causes unscheduled hepatocyte proliferation. Genes Dev 2004; 18:88–98.

    Article  CAS  PubMed  Google Scholar 

  38. Liu Z, Diaz LA, Haas AL et al. cDNA cloning of a novel human ubiquitin carrier protein. An antigenic domain specifically recognized by endemic pemphigus foliaceus autoantibodies is encoded in a secondary reading frame of this human epidermal transcript. J Biol Chem 1992; 267:15829–35.

    CAS  PubMed  Google Scholar 

  39. Tedesco D, Zhang J, Trinh L et al. The ubiquitin-conjugating enzyme E2-E PF is overexpressed in primary breast cancer and modulates sensitivity to topoisomerase II inhibition. Neoplasia 2007; 9:601–13.

    Article  CAS  PubMed  Google Scholar 

  40. Jung CR, Hwang KS, Yoo J et al. E2-E PF UCP targets pVHL for degradation and associates with tumor growth and metastasis. Nature Med 2006; 12:809–16.

    Article  CAS  PubMed  Google Scholar 

  41. Yu H. Cdc20: a WD40 activator for a cell cycle degradation machine. Mol Cell 2007; 27:3–16.

    Article  CAS  PubMed  Google Scholar 

  42. Visintin R, Prinz S, Amon A. CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis. Science 1997; 278:460–463.

    Article  CAS  PubMed  Google Scholar 

  43. Zheng N, Schulman BA, Song L et al. Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature 2002; 416:703–9.

    Article  CAS  PubMed  Google Scholar 

  44. Tang Z, Li B, Bharadwaj R et al. APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex. Mol Biol Cell 2001; 12:3839–51.

    CAS  PubMed  Google Scholar 

  45. Eddins MJ, Carlile CM, Gomez KM et al. Mms2-Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation. Nature Struct Mol Biol 2006; 13:915–20.

    Article  CAS  Google Scholar 

  46. Kaelin WG. Von Hippel-Lindau disease. Annu Rev Pathol 2007; 2:145–73.

    Article  CAS  PubMed  Google Scholar 

  47. Reyes-Turcu FE, Ventii KH, Wilkinson KD. Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Annu Rev Biochem 2009; 78:363–97.

    Article  CAS  PubMed  Google Scholar 

  48. Komander D, Clague MJ, Urbé S. Breaking the chains: structures and functions of deubiquitinases. Nat Rev Mol Cell Biol 2009; 10:550–63.

    Article  CAS  PubMed  Google Scholar 

  49. Song L, Rape M. Reverse the curse—the role of deubiquitination in cell cycle control. Curr Opin Cell Biol 2007; 20:156–63.

    Article  CAS  Google Scholar 

  50. Crosas B, Hanna J, Kirkpatrick DS et al. Ubiquitin chains are remodeled at the proteasome by opposing ubiquitin ligase and deubiquitinating activites. Cell 2006; 127:1401–13.

    Article  CAS  PubMed  Google Scholar 

  51. Yao T, Song L, Xu W et al. Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1. Nat Cell Biol 2006; 8:994–1002.

    Article  CAS  PubMed  Google Scholar 

  52. Beal R, Deveraux Q, Xia G et al. Surface hydrophobic residues of multiubiquitin chains essential for proteolytic targeting. Proc Natl Acad Sci USA 1996; 93:861–6.

    Article  CAS  PubMed  Google Scholar 

  53. Ortolan TG, Tongaonkar P, Lambertson D et al. The DNA repair protein rad23 is a negative regulator of multi-ubiquitin chain assembly. Nat Cell Biol 2000; 2:601–8.

    Article  CAS  PubMed  Google Scholar 

  54. Thoma CR, Toso A, Gutbrodt KL et al. VHL loss causes spindle misorientation and chromosome instability. Nat Cell Biol 2009; 11:994–1001.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California, 94720, USA

    Michael Rape

Authors
  1. Michael Rape
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Biology, Division of Immunology, University of Konstanz, Konstanz, Germany

    Marcus Groettrup PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Rape, M. (2010). Assembly of K11-Linked Ubiquitin Chains by the Anaphase-Promoting Complex. In: Groettrup, M. (eds) Conjugation and Deconjugation of Ubiquitin Family Modifiers. Subcellular Biochemistry, vol 54. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6676-6_9

Download citation

Publish with us

Policies and ethics

Search

Navigation