The Inhibitor of Apoptosis, cIAP2, Functions as a Ubiquitin-Protein Ligase and Promotes in VitroMonoubiquitination of Caspases 3 and 7*
- Han-kuei Huang‡,
- Claudio A. P. Joazeiro‡,
- Emanuela Bonfoco§,
- Shinji Kamada‡,
- Joel D. Leverson‡ and
- Tony Hunter‡¶
- From the ‡Molecular Biology and Virology Laboratory, The Salk Institute for Biological Studies and the§Department of Immunology, The Scripps Research Institute, La Jolla, California 92037
Abstract
The inhibitor of apoptosis, cIAP2, contains a putative Ring finger motif at the C terminus. Using in vitro ubiquitination assays, we found that the Ring finger of cIAP2 alone possesses intrinsic ubiquitin ligase activity and promotes substrate-independent ubiquitination. It also promotes ubiquitination of caspases 3 and 7 but not caspase-1. The Ring fingers of c-Cbl and Apc11 failed to promote caspase-7 ubiquitination, suggesting that the Ring finger of cIAP2 itself is involved in substrate recognition.
Footnotes
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↵* This work was supported by Fellowship DRG-1531 from the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation (to H.-k. H.), by Fellowship 2-41-98 from the American Cancer Society, California Division (to C. A. P. J.), by Grant PF9922801CCG from the American Cancer Society (to J. D. L.), and by Public Health Service Grants CA39780 and CA82683 from the National Cancer Institute (to T. H.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵¶ Frank and Else Schilling American Cancer Society Professor. To whom correspondence should be addressed: Molecular Biology and Virology Laboratory, The Salk Inst. for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA 92037. Tel.: 858-453-4100; Fax: 858-457-4765; E-mail: hunter@salk.edu.
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Published, JBC Papers in Press, June 20, 2000, DOI 10.1074/jbc.C000199200
- Abbreviations:
- IAP
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inhibitor(s) of apoptosis
- BIR
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baculoviral IAP repeat
- CARD
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caspase-recruitment domain
- HECT
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homologous to E6-AP C terminus
- GST
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glutathioneS-transferase
- Casp
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caspase
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- Received March 26, 2000.
- Revision received June 18, 2000.
- The American Society for Biochemistry and Molecular Biology, Inc.
