Article abstract
Nature Cell Biology 4, 432 - 438 (2002)
Published online: 20 May 2002 | doi:10.1038/ncb795
There is an Erratum (July 2002) associated with this Article.
Regulation of Drosophila IAP1 degradation and apoptosis by reaper and ubcD1
Hyung Don Ryoo1, Andreas Bergmann2, Hedva Gonen3, Aaron Ciechanover3 & Hermann Steller1
Abstract
Cell death in higher organisms is negatively regulated by Inhibitor of Apoptosis Proteins (IAPs), which contain a ubiquitin ligase motif, but how ubiquitin-mediated protein degradation is regulated during apoptosis is poorly understood. Here, we report that Drosophila melanogaster IAP1 (DIAP1) auto-ubiquitination and degradation is actively regulated by Reaper (Rpr) and UBCD1. We show that Rpr, but not Hid (head involution defective), promotes significant DIAP1 degradation. Rpr-mediated DIAP1 degradation requires an intact DIAP1 RING domain. Among the mutations affecting ubiquitination, we found ubcD1, which suppresses rpr-induced apoptosis. UBCD1 and Rpr specifically bind to DIAP1 and stimulate DIAP1 auto-ubiquitination in vitro. Our results identify a novel function of Rpr in stimulating DIAP1 auto-ubiquitination through UBCD1, thereby promoting its degradation.
- Howard Hughes Medical Institute, Strang Laboratory of Cancer Research, The Rockefeller University Box 252, 1230 York Ave. New York, NY 10021, USA
- Department of Biochemistry and Molecular Biology, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA
- Department of Biochemistry, Faculty of Medicine, Technion, Haifa 31096, Israel
Correspondence to: Hermann Steller1 e-mail: steller@mail.rockefeller.edu
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