Smac/Diablo antagonizes ubiquitin ligase activity of inhibitor of apoptosis proteins
Citation:
Creagh EM, Murphy BM, Duriez PJ, Duckett CS, Martin SJ, Smac/Diablo antagonizes ubiquitin ligase activity of inhibitor of apoptosis proteins, JOURNAL OF BIOLOGICAL CHEMISTRY, 279, 26, 2004, 26906, 26914Download Item:
Abstract:
Inhibitor of apoptosis proteins (IAPs) can block apoptosis through binding to active caspases and antagonizing their function. IAP function can be neutralized by Smac/Diablo, an IAP-binding protein that is released from mitochondria during apoptosis. In addition to their ability to interact with caspases, certain IAPs also display ubiquitin-protein isopeptide ligase activity because of the presence of a RING domain. However, it is not known whether the ubiquitin-protein isopeptide ligase activities of human IAPs contribute to their apoptosis inhibitory activity or whether this IAP property can be modulated through association with Smac/Diablo. Here we demonstrate that the ubiquitin ligase activities of XIAP, and to a lesser extent c-IAP-1 and c-IAP2, are potently repressed through binding to Smac/Diablo. We also show that mutation of the XIAP RING domain rendered this IAP a less effective inhibitor of apoptosis, suggesting that the ubiquitin ligase activity of XIAP contributes to its anti-apoptotic function. These data suggest that Smac/Diablo potentiates apoptosis by simultaneously antagonizing caspase-IAP interactions and repressing IAP ubiquitin ligase activities.
Sponsor
Grant Number
European Union (EU)
QLG1- 1999-00739
Science Foundation Ireland (SFI)
PI1/B038
Health Research Board (HRB)
Author's Homepage:
http://people.tcd.ie/martinsjhttp://people.tcd.ie/ecreagh
Description:
PUBLISHEDPMID: 15078891
Author: MARTIN, SEAMUS; CREAGH, EMMA
Sponsor:
European Union (EU)Science Foundation Ireland (SFI)
Health Research Board (HRB)
Type of material:
Journal ArticleCollections
Series/Report no:
JOURNAL OF BIOLOGICAL CHEMISTRY279
26
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Full text availableDOI:
http://dx.doi.org/10.1074/jbc.M313859200Metadata
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