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Smac/Diablo antagonizes ubiquitin ligase activity of inhibitor of apoptosis proteins

Smac/Diablo antagonizes ubiquitin ligase activity of inhibitor of apoptosis proteins
Smac/Diablo antagonizes ubiquitin ligase activity of inhibitor of apoptosis proteins
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
0021-9258
26906-26914
Creagh, Emma M.
c5311521-65cc-46df-8f7d-d6416aa05a95
Murphy, Brona M.
df924139-baf2-4f21-b541-572f265f9a4b
Duriez, Patrick J.
523004b2-256b-4e62-b394-100bda55adf0
Duckett, Colin S.
d7c25aad-ad39-42a0-b328-9cd199b7e26f
Martin, Seamus J.
3df02649-5634-44da-834d-098937a7ae5b
Creagh, Emma M.
c5311521-65cc-46df-8f7d-d6416aa05a95
Murphy, Brona M.
df924139-baf2-4f21-b541-572f265f9a4b
Duriez, Patrick J.
523004b2-256b-4e62-b394-100bda55adf0
Duckett, Colin S.
d7c25aad-ad39-42a0-b328-9cd199b7e26f
Martin, Seamus J.
3df02649-5634-44da-834d-098937a7ae5b

Creagh, Emma M., Murphy, Brona M., Duriez, Patrick J., Duckett, Colin S. and Martin, Seamus J. (2004) Smac/Diablo antagonizes ubiquitin ligase activity of inhibitor of apoptosis proteins. The Journal of Biological Chemistry, 279 (26), 26906-26914. (doi:10.1074/jbc.M313859200). (PMID:15078891)

Record type: Article

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

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Published date: 25 June 2004

Identifiers

Local EPrints ID: 164805
URI: http://eprints.soton.ac.uk/id/eprint/164805
ISSN: 0021-9258
PURE UUID: b76886f1-b173-4ee9-b41c-68ec8641c826

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Date deposited: 05 Oct 2010 07:29
Last modified: 16 Jul 2019 23:52

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