The X-linked mammalian inhibitor of apoptosis protein (XIAP) has been shown to bind several partners. These partners include caspase 3, caspase 9, DIABLO/Smac, HtrA2/Omi, TAB1, the bone morphogenetic protein receptor, and a presumptive E2 ubiquitin-conjugating enzyme. In addition, we show here that XIAP can bind to itself. To determine which of these interactions are required for it to inhibit apoptosis, we generated point mutant XIAP proteins and correlated their ability to bind other proteins with their ability to inhibit apoptosis. ∂RING point mutants of XIAP were as competent as their full-length counterparts in inhibiting apoptosis, although impaired in their ability to oligomerize with full-length XIAP. Triple point mutants, unable to bind caspase 9, caspase 3, and DIABLO/HtrA2/Omi, were completely ineffectual in inhibiting apoptosis. However, point mutants that had lost the ability to inhibit caspase 9 and caspase 3 but retained the ability to inhibit DIABLO were still able to inhibit apoptosis, demonstrating that IAP antagonism is required for apoptosis to proceed following UV irradiation.
Skip Nav Destination
Article navigation
1 April 2002
Article|
April 01 2002
The anti-apoptotic activity of XIAP is retained upon mutation of both the caspase 3– and caspase 9–interacting sites
John Silke,
John Silke
1The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia
Search for other works by this author on:
Christine J. Hawkins,
Christine J. Hawkins
3Department of Haematology and Oncology, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville 3052 Australia.
4Department of Paediatrics, University of Melbourne, Parkville 3050 Australia
Search for other works by this author on:
Paul G. Ekert,
Paul G. Ekert
1The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia
Search for other works by this author on:
Joanne Chew,
Joanne Chew
5Institute of Molecular and Cell Biology, National University of Singapore, Singapore 117609
Search for other works by this author on:
Catherine L. Day,
Catherine L. Day
2Biochemistry Department, University of Otago, Dunedin, New Zealand
Search for other works by this author on:
Miha Pakusch,
Miha Pakusch
1The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia
Search for other works by this author on:
Anne M. Verhagen,
Anne M. Verhagen
1The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia
Search for other works by this author on:
David L. Vaux
David L. Vaux
1The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia
Search for other works by this author on:
John Silke
1The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia
Christine J. Hawkins
3Department of Haematology and Oncology, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville 3052 Australia.
4Department of Paediatrics, University of Melbourne, Parkville 3050 Australia
Paul G. Ekert
1The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia
Joanne Chew
5Institute of Molecular and Cell Biology, National University of Singapore, Singapore 117609
Catherine L. Day
2Biochemistry Department, University of Otago, Dunedin, New Zealand
Miha Pakusch
1The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia
Anne M. Verhagen
1The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia
David L. Vaux
1The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia
Address correspondence to John Silke, The Walter and Eliza Hall Institute, c/o Royal Melbourne Hospital Post Office, Victoria 3050, Australia. Tel.: 61-3-9345-2548. Fax: 61-3-9347-0852. E-mail: [email protected]
*
Abbreviations used in this paper: IAP, inhibitor of apoptosis protein; BIR, baculoviral IAP repeat; TNF, tumor necrosis factor; TRAF, TNF receptor associated factors; XIAP, X-linked mammalian inhibitor of apoptosis protein.
Received:
August 17 2001
Revision Received:
February 13 2002
Accepted:
February 25 2002
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2002
J Cell Biol (2002) 157 (1): 115–124.
Article history
Received:
August 17 2001
Revision Received:
February 13 2002
Accepted:
February 25 2002
Citation
John Silke, Christine J. Hawkins, Paul G. Ekert, Joanne Chew, Catherine L. Day, Miha Pakusch, Anne M. Verhagen, David L. Vaux; The anti-apoptotic activity of XIAP is retained upon mutation of both the caspase 3– and caspase 9–interacting sites . J Cell Biol 1 April 2002; 157 (1): 115–124. doi: https://doi.org/10.1083/jcb.200108085
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionEmail alerts
Advertisement
Advertisement