A Giant Ubiquitin-conjugating Enzyme Related to IAP Apoptosis Inhibitors

A Giant Ubiquitin-conjugating Enzyme Related to IAP Apoptosis Inhibitors Ubiquitin-conjugating enzymes (UBC) catalyze the covalent attachment of ubiquitin to target proteins and are distinguished by the presence of a UBC domain required for catalysis. Previously identified members of this enzyme family are small proteins and function primarily in selective proteolysis pathways. Here we describe BRUCE (BIR repeat containing ubiquitin-conjugating enzyme), a giant (528-kD) ubiquitin-conjugating enzyme from mice. BRUCE is membrane associated and localizes to the Golgi compartment and the vesicular system. Remarkably, in addition to being an active ubiquitin-conjugating enzyme, BRUCE bears a baculovirus inhibitor of apoptosis repeat (BIR) motif, which to this date has been exclusively found in apoptosis inhibitors of the IAP-related protein family. The BIR motifs of IAP proteins are indispensable for their anti–cell death activity and are thought to function through protein–protein interaction. This suggests that BRUCE may combine properties of IAP-like proteins and ubiquitin-conjugating enzymes and indicates that the family of IAP-like proteins is structurally and functionally more diverse than previously expected. Footnotes The work by H.-P. Hauser was done in the former laboratory of S. Jentsch in Tübingen. We thank T. Hoppe for important contributions to this study; M. Scheffner, G. Banting, R. Brandt, B. Dobberstein, and A. Clement for providing materials; M. Scheffner for help and advice for thioester experiments; F. Weinreich for help with DNA sequencing; E. Löser and P. Hubbe for technical assistance; and H. Ulrich for comments on the manuscript. H.-P. Hauser and M. Bardroff contributed equally to this work. Address all correspondence to Dr. Stefan Jentsch, ZMBH, Zentrum für Molekulare Biologie, Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany. Tel.: +49 6221 548716. Fax: 49 6221 545891. E-mail: jentsch@zmbh.uni-heidelberg.de The present address of Hans-Peter Hauser is Dade Behring, Inc., M 106, P.O. Box 1149, 35001 Marburg, Germany. The present address of Michael Bardroff is MorphoSys GmbH, Am Klopferspitz 19, 82152 Martinsried/Munich, Germany. Abbreviations used in this paper: BIR baculovirus inhibitor of apoptosis repeat BRUCE BIR repeat containing ubiquitin-conjugating enzyme E1 ubiquitin-activating enzyme IAP inhibitor of apoptosis protein NAIP neuronal apoptosis inhibitor protein ORF open reading frame UBC ubiquitin-conjugating enzyme Submitted: 6 April 1998 Revision received 27 April 1998 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Cell Biology Rockefeller University Press

A Giant Ubiquitin-conjugating Enzyme Related to IAP Apoptosis Inhibitors

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Publisher
Rockefeller University Press
Copyright
© 1998 Rockefeller University Press
ISSN
0021-9525
eISSN
1540-8140
D.O.I.
10.1083/jcb.141.6.1415
Publisher site
See Article on Publisher Site

Abstract

Ubiquitin-conjugating enzymes (UBC) catalyze the covalent attachment of ubiquitin to target proteins and are distinguished by the presence of a UBC domain required for catalysis. Previously identified members of this enzyme family are small proteins and function primarily in selective proteolysis pathways. Here we describe BRUCE (BIR repeat containing ubiquitin-conjugating enzyme), a giant (528-kD) ubiquitin-conjugating enzyme from mice. BRUCE is membrane associated and localizes to the Golgi compartment and the vesicular system. Remarkably, in addition to being an active ubiquitin-conjugating enzyme, BRUCE bears a baculovirus inhibitor of apoptosis repeat (BIR) motif, which to this date has been exclusively found in apoptosis inhibitors of the IAP-related protein family. The BIR motifs of IAP proteins are indispensable for their anti–cell death activity and are thought to function through protein–protein interaction. This suggests that BRUCE may combine properties of IAP-like proteins and ubiquitin-conjugating enzymes and indicates that the family of IAP-like proteins is structurally and functionally more diverse than previously expected. Footnotes The work by H.-P. Hauser was done in the former laboratory of S. Jentsch in Tübingen. We thank T. Hoppe for important contributions to this study; M. Scheffner, G. Banting, R. Brandt, B. Dobberstein, and A. Clement for providing materials; M. Scheffner for help and advice for thioester experiments; F. Weinreich for help with DNA sequencing; E. Löser and P. Hubbe for technical assistance; and H. Ulrich for comments on the manuscript. H.-P. Hauser and M. Bardroff contributed equally to this work. Address all correspondence to Dr. Stefan Jentsch, ZMBH, Zentrum für Molekulare Biologie, Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany. Tel.: +49 6221 548716. Fax: 49 6221 545891. E-mail: jentsch@zmbh.uni-heidelberg.de The present address of Hans-Peter Hauser is Dade Behring, Inc., M 106, P.O. Box 1149, 35001 Marburg, Germany. The present address of Michael Bardroff is MorphoSys GmbH, Am Klopferspitz 19, 82152 Martinsried/Munich, Germany. Abbreviations used in this paper: BIR baculovirus inhibitor of apoptosis repeat BRUCE BIR repeat containing ubiquitin-conjugating enzyme E1 ubiquitin-activating enzyme IAP inhibitor of apoptosis protein NAIP neuronal apoptosis inhibitor protein ORF open reading frame UBC ubiquitin-conjugating enzyme Submitted: 6 April 1998 Revision received 27 April 1998

Journal

The Journal of Cell BiologyRockefeller University Press

Published: Jun 15, 1998

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