Regulation of Apoptosis and Cytokinesis by the Anti-apoptotic E2/E3 Ubiquitin-Ligase BRUCE

Conference paper
Part of the Ernst Schering Foundation Symposium Proceedings book series (SCHERING FOUND, volume 2008/1)


Members of the inhibitor of apoptosis protein (IAP) family are key regulators of apoptosis as they bind and inhibit caspases and other pro-apoptotic factors. Recent findings suggest that these proteins play additional roles, e.g., in cell cycle regulation, angiogenesis, and carcinogenesis. Here, we review the function of BRUCE (BIR repeat-containing ubiquitin-conjugating enzyme), an unusual 528-kDa IAP with ubiquitin ligase activity, and describe its role in apoptosis and cytokinesis. Additionally, we discuss how these seemingly unrelated functions might be linked.


Ubiquitin Ligase Apoptosis Regulation Ubiquitin Ligase Activity Intercellular Bridge Chromosomal Passenger Complex 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Albertson R, Riggs B, Sullivan W (2005) Membrane traffic: a driving force in cytokinesis. Trends Cell Biol 15:92–101CrossRefPubMedGoogle Scholar
  2. Arama E, Agapite J, Steller H (2003) Caspase activity and a specific cytochrome C are required for sperm differentiation in Drosophila. Dev Cell 4:687–697CrossRefPubMedGoogle Scholar
  3. Arama E, Bader M, Rieckhof GE, Steller H (2007) A ubiquitin ligase complex regulates caspase activation during sperm differentiation in Drosophila. PLoS Biol 5:e251CrossRefPubMedGoogle Scholar
  4. Banks DP, Plescia J, Altieri DC, Chen J, Rosenberg SH, Zhang H, Ng SC (2000) Survivin does not inhibit caspase-3 activity. Blood 96:4002–4003PubMedGoogle Scholar
  5. Bardroff M (1997) Charakterisierung eines neuartigen Proteins der Maus mit Homologie zu Ubiquitin-Konjugationsenzymen und Apoptose-Inhibitoren. Eberhard-Karls-Universität, TübingenGoogle Scholar
  6. Bartke T, Pohl C, Pyrowolakis G, Jentsch S (2004) Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase. Mol Cell 14:801–811CrossRefPubMedGoogle Scholar
  7. Carlton JG, Martin-Serrano J (2007) Parallels between cytokinesis and retroviral budding: a role for the ESCRT machinery. Science 316:1908–1912CrossRefPubMedGoogle Scholar
  8. Chai J, Shiozaki E, Srinivasula SM, Wu Q, Datta P, Alnemri ES, Shi Y (2001) Structural basis of caspase-7 inhibition by XIAP. Cell 104:769–780CrossRefPubMedGoogle Scholar
  9. Chen Z, Naito M, Hori S, Mashima T, Yamori T, Tsuruo T (1999) A human IAP-family gene, apollon, expressed in human brain cancer cells. Biochem Biophys Res Commun 264:847–854CrossRefPubMedGoogle Scholar
  10. Clague MJ, Urbé S (2006) Endocytosis: the DUB version. Trends Cell Biol 16:551–559CrossRefPubMedGoogle Scholar
  11. Crnkovic-Mertens I, Semzow J, Hoppe-Seyler F, Butz K (2006) Isoform-specific silencing of the Livin gene by RNA interference defines Livin beta as key mediator of apoptosis inhibition in HeLa cells. J Mol Med 84:232–240CrossRefPubMedGoogle Scholar
  12. Diamonti AJ, Guy PM, Ivanof C, Wong K, Sweeney C, Carraway KL 3rd (2002) An RBCC protein implicated in maintenance of steady-state neuregulin receptor levels. Proc Natl Acad Sci U S A 99:2866–2871CrossRefPubMedGoogle Scholar
  13. Ditzel M, Meier P (2002) IAP degradation: decisive blow or altruistic sacrifice? Trends Cell Biol 12:449–452CrossRefPubMedGoogle Scholar
  14. Grenfell SJ, Trausch-Azar JS, Handley-Gearhart PM, Ciechanover A, Schwartz AL (1994) Nuclear localization of the ubiquitin-activating enzyme, E1, is cell-cycle-dependent. Biochem J 300:701–708PubMedGoogle Scholar
  15. Gromley A, Yeaman C, Rosa J, Redick S, Chen CT, Mirabelle S, Guha M, Sillibourne J, Doxsey SJ (2005) Centriolin anchoring of exocyst and SNARE complexes at the midbody is required for secretory-vesicle-mediated abscission. Cell 123:75–87CrossRefPubMedGoogle Scholar
  16. Hao Y, Sekine K, Kawabata A, Nakamura H, Ishioka T, Ohata H, Katayama R, Hashimoto C, Zhang X, Noda T, Tsuruo T, Naito M (2004) Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function. Nat Cell Biol 6:849–860CrossRefPubMedGoogle Scholar
  17. Hauser H (1992) Charakterisierung von UbcM1, einem Vertreter einer neuen Klasse von Ubiquitin-Konjugationsenzmyen in Vertebraten. Eberhard-Karls-Universität, TübingenGoogle Scholar
  18. Hauser HP, Bardroff M, Pyrowolakis G, Jentsch S (1998) A giant ubiquitin-conjugating enzyme related to IAP apoptosis inhibitors. J Cell Biol 141:1415–1422CrossRefPubMedGoogle Scholar
  19. Hinds MG, Norton RS, Vaux DL, Day CL (1999) Solution structure of a baculoviral inhibitor of apoptosis (IAP) repeat. Nat Struct Biol 6:648–651CrossRefPubMedGoogle Scholar
  20. Huang Y, Park YC, Rich RL, Segal D, Myszka DG, Wu H (2001) Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain. Cell 104:781–790PubMedGoogle Scholar
  21. Li F, Ackermann EJ, Bennett CF, Rothermel AL, Plescia J, Tognin S, Villa A, Marchisio PC, Altieri DC (1999) Pleiotropic cell-division defects and apoptosis induced by interference with survivin function. Nat Cell Biol 1:461–466CrossRefPubMedGoogle Scholar
  22. Lotz K, Pyrowolakis G, Jentsch S (2004) BRUCE, a giant E2/E3 ubiquitin ligase and inhibitor of apoptosis protein of the trans-Golgi network, is required for normal placenta development and mouse survival. Mol Cell Biol 24:9339–9350CrossRefPubMedGoogle Scholar
  23. Peränen J, Auvinen P, Virta H, Wepf R, Simons K (1996) Rab8 promotes polarized membrane transport through reorganization of actin and microtubules in fibroblasts. J Cell Biol 135:153–167CrossRefPubMedGoogle Scholar
  24. Pines J (2006) Mitosis: a matter of getting rid of the right protein at the right time. Trends Cell Biol 16:55–63CrossRefPubMedGoogle Scholar
  25. Pohl C, Jentsch S (2008) Final stages of cytokinesis and midbody ring formation are controlled by BRUCE. Cell 132:832–845CrossRefPubMedGoogle Scholar
  26. Potapova TA, Daum JR, Pittman BD, Hudson JR, Jones TN, Satinover DL, Stukenberg PT, Gorbsky GJ (2006) The reversibility of mitotic exit in vertebrate cells. Nature 440:954–958CrossRefPubMedGoogle Scholar
  27. Qiu XB, Goldberg AL (2002) Nrdp1/FLRF is a ubiquitin ligase promoting ubiquitination and degradation of the epidermal growth factor receptor family member, ErbB3. Proc Natl Acad Sci U S A 99:14843–14848CrossRefPubMedGoogle Scholar
  28. Qiu XB, Markant SL, Yuan J, Goldberg AL (2004) Nrdp1-mediated degradation of the gigantic IAP, BRUCE, is a novel pathway for triggering apoptosis. EMBO J 23:800–810CrossRefPubMedGoogle Scholar
  29. Riedl SJ, Renatus M, Schwarzenbacher R, Zhou Q, Sun C, Fesik SW, Liddington RC, Salvesen GS (2001) Structural basis for the inhibition of caspase-3 by XIAP. Cell 104:791–800CrossRefPubMedGoogle Scholar
  30. Row PE, Prior IA, McCullough J, Clague MJ, Urbe S (2006) The ubiquitin isopeptidase UBPY regulates endosomal ubiquitin dynamics and is essential for receptor down-regulation. J Biol Chem 281:12618–12624CrossRefPubMedGoogle Scholar
  31. Salvesen GS, Duckett CS (2002) IAP proteins: blocking the road to death's door. Nat Rev Mol Cell Biol 3:401–410CrossRefPubMedGoogle Scholar
  32. Samuel T, Okada K, Hyer M, Welsh K, Zapata JM, Reed JC (2005) cIAP1 Localizes to the nuclear compartment and modulates the cell cycle. Cancer Res 65:210–218PubMedGoogle Scholar
  33. Song Z, Yao X, Wu M (2003) Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during taxol-induced apoptosis. J Biol Chem 278:23130–23140CrossRefPubMedGoogle Scholar
  34. Urbé S, Huber LA, Zerial M, Tooze SA, Parton RG (1993) Rab11, a small GTPase associated with both constitutive and regulated secretory pathways in PC12 cells. FEBS Lett 334:175–182CrossRefPubMedGoogle Scholar
  35. Verhagen AM, Coulson EJ, Vaux DL (2001) Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs. Genome Biol 2:REVIEWS3009Google Scholar
  36. Vernooy SY, Chow V, Su J, Verbrugghe K, Yang J, Cole S, Olson MR, Hay BA (2002) Drosophila Bruce can potently suppress Rpr- and Grim-dependent but not Hid-dependent cell death. Curr Biol 12:1164–1168CrossRefPubMedGoogle Scholar
  37. Wojcik C, Paweletz N, Schroeter D (1995) Localization of proteasomal antigens during different phases of the cell cycle in HeLa cells. Eur J Cell Biol 68:191–198PubMedGoogle Scholar
  38. Wu X, Yen L, Irwin L, Sweeney C, Carraway KL 3rd (2004) Stabilization of the E3 ubiquitin ligase Nrdp1 by the deubiquitinating enzyme USP8. Mol Cell Biol 24:7748–57CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Department of Molecular Cell BiologyMax Planck Institute of BiochemistryMartinsriedGermany

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