Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published February 7, 2003 | Published
Journal Article Open

Reaper is regulated by IAP-mediated ubiquitination

Abstract

In most cases, apoptotic cell death culminates in the activation of the caspase family of cysteine proteases, leading to the orderly dismantling and elimination of the cell. The IAPs (inhibitors of apoptosis) comprise a family of proteins that oppose caspases and thus act to raise the apoptotic threshold. Disruption of IAP-mediated caspase inhibition has been shown to be an important activity for pro-apoptotic proteins in Drosophila (Reaper, HID, and Grim) and in mammalian cells (Smac/DIABLO and Omi/HtrA2). In addition, in the case of the fly, these proteins are able to stimulate the ubiquitination and degradation of IAPs by a mechanism involving the ubiquitin ligase activity of the IAP itself. In this report, we show that the Drosophila RHG proteins (Reaper, HID, and Grim) are themselves substrates for IAP-mediated ubiquitination. This ubiquitination of Reaper requires IAP ubiquitin-ligase activity and a stable interaction between Reaper and the IAP. Additionally, degradation of Reaper can be blocked by mutating its potential ubiquitination sites. Most importantly, we also show that regulation of Reaper by ubiquitination is a significant factor in determining its biological activity. These data demonstrate a novel function for IAPs and suggest that IAPs and Reaper-like proteins mutually control each other's abundance.

Additional Information

© 2003 The American Society for Biochemistry and Molecular Biology, Inc. Received for publication, September 23, 2002, and in revised form, November 19, 2002. Published, JBC Papers in Press, November 20, 2002. We thank Dr. Kristin White (Harvard/MGH) for providing the pIE3/DIAP1 clone. We are grateful to Dr. Rick Fehon and Rima Kulikauskas for assistance and space for insect cell culture.

Attached Files

Published - OLSjbc03.pdf

Files

OLSjbc03.pdf
Files (298.9 kB)
Name Size Download all
md5:447142a863681b32d4dfaabd1146b9b5
298.9 kB Preview Download

Additional details

Created:
August 22, 2023
Modified:
October 16, 2023