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Article: Heat-shock protein 70 antagonizes apoptosis-inducing factor

TitleHeat-shock protein 70 antagonizes apoptosis-inducing factor
Authors
Issue Date2001
Citation
Nature Cell Biology, 2001, v. 3, n. 9, p. 839-843 How to Cite?
AbstractHeat-shock protein 70 (Hsp70) has been reported to block apoptosis by binding apoptosis protease activating factor-1 (Apaf-1), thereby preventing constitution of the apoptosome, the Apaf-1/cytochrome c/caspase-9 activation complex12. Here we show that overexpression of Hsp70 protects Apaf-1-/- cells against death induced by serum withdrawal, indicating that Apaf-1 is not the only target of the anti-apoptotic action of Hsp70. We investigated the effect of Hsp70 on apoptosis mediated by the caspase-independent death effector apoptosis inducing factor (AIF), which is a mitochondrial intermembrane flavoprotein. In a cell-free system, Hsp70 prevented the AIF-induced chromatin condensation of purified nuclei. Hsp70 specifically interacted with AIF, as shown by ligand blots and co-immunoprecipitation. Cells overexpressing Hsp70 were protected against the apoptogenic effects of AIF targeted to the extramitochondrial compartment. In contrast, an anti-sense Hsp70 complementary DNA, which reduced the expression of endogenous Hsp70, increased sensitivity to the lethal effect of AIF. The ATP-binding domain of Hsp70 seemed to be dispensable for inhibiting cell death induced by serum withdrawal, AIF binding and AIF inhibition, although it was required for Apaf-1 binding. Together, our data indicate that Hsp70 can inhibit by interfering with target proteins other than Apaf-1, one of which is AIF.
Persistent Identifierhttp://hdl.handle.net/10722/291714
ISSN
2023 Impact Factor: 17.3
2023 SCImago Journal Rankings: 8.913
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorRavagnan, Luigi-
dc.contributor.authorGurbuxani, Sandeep-
dc.contributor.authorSusin, Santos A.-
dc.contributor.authorMaisse, Carine-
dc.contributor.authorDaugas, Eric-
dc.contributor.authorZamzami, Naoufal-
dc.contributor.authorMak, Tak-
dc.contributor.authorJäättelä, Marja-
dc.contributor.authorPenninger, Josef M.-
dc.contributor.authorGarrido, Carmen-
dc.contributor.authorKroemer, Guido-
dc.date.accessioned2020-11-17T14:54:57Z-
dc.date.available2020-11-17T14:54:57Z-
dc.date.issued2001-
dc.identifier.citationNature Cell Biology, 2001, v. 3, n. 9, p. 839-843-
dc.identifier.issn1465-7392-
dc.identifier.urihttp://hdl.handle.net/10722/291714-
dc.description.abstractHeat-shock protein 70 (Hsp70) has been reported to block apoptosis by binding apoptosis protease activating factor-1 (Apaf-1), thereby preventing constitution of the apoptosome, the Apaf-1/cytochrome c/caspase-9 activation complex12. Here we show that overexpression of Hsp70 protects Apaf-1-/- cells against death induced by serum withdrawal, indicating that Apaf-1 is not the only target of the anti-apoptotic action of Hsp70. We investigated the effect of Hsp70 on apoptosis mediated by the caspase-independent death effector apoptosis inducing factor (AIF), which is a mitochondrial intermembrane flavoprotein. In a cell-free system, Hsp70 prevented the AIF-induced chromatin condensation of purified nuclei. Hsp70 specifically interacted with AIF, as shown by ligand blots and co-immunoprecipitation. Cells overexpressing Hsp70 were protected against the apoptogenic effects of AIF targeted to the extramitochondrial compartment. In contrast, an anti-sense Hsp70 complementary DNA, which reduced the expression of endogenous Hsp70, increased sensitivity to the lethal effect of AIF. The ATP-binding domain of Hsp70 seemed to be dispensable for inhibiting cell death induced by serum withdrawal, AIF binding and AIF inhibition, although it was required for Apaf-1 binding. Together, our data indicate that Hsp70 can inhibit by interfering with target proteins other than Apaf-1, one of which is AIF.-
dc.languageeng-
dc.relation.ispartofNature Cell Biology-
dc.titleHeat-shock protein 70 antagonizes apoptosis-inducing factor-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/ncb0901-839-
dc.identifier.pmid11533664-
dc.identifier.scopuseid_2-s2.0-17944366977-
dc.identifier.volume3-
dc.identifier.issue9-
dc.identifier.spage839-
dc.identifier.epage843-
dc.identifier.isiWOS:000170979600018-
dc.identifier.issnl1465-7392-

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