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Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis

In sympathetic neurons, unlike most nonneuronal cells, growth factor withdrawal–induced apoptosis requires the development of competence in addition to cytochrome c release to activate caspases. Thus, although most nonneuronal cells die rapidly with cytosolic cytochrome c alone, sympathetic neurons...

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Detalles Bibliográficos
Autores principales: Potts, Patrick Ryan, Singh, Shweta, Knezek, Malia, Thompson, Craig B., Deshmukh, Mohanish
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173693/
https://www.ncbi.nlm.nih.gov/pubmed/14623868
http://dx.doi.org/10.1083/jcb.200307130
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author Potts, Patrick Ryan
Singh, Shweta
Knezek, Malia
Thompson, Craig B.
Deshmukh, Mohanish
author_facet Potts, Patrick Ryan
Singh, Shweta
Knezek, Malia
Thompson, Craig B.
Deshmukh, Mohanish
author_sort Potts, Patrick Ryan
collection PubMed
description In sympathetic neurons, unlike most nonneuronal cells, growth factor withdrawal–induced apoptosis requires the development of competence in addition to cytochrome c release to activate caspases. Thus, although most nonneuronal cells die rapidly with cytosolic cytochrome c alone, sympathetic neurons are remarkably resistant unless they develop competence. We have identified endogenous X-linked inhibitor of apoptosis protein (XIAP) as the essential postcytochrome c regulator of caspase activation in these neurons. In contrast to wild-type neurons that are resistant to injection of cytochrome c, XIAP-deficient neurons died rapidly with cytosolic cytochrome c alone. Surprisingly, the release of endogenous Smac was not sufficient to overcome the XIAP resistance in sympathetic neurons. In contrast, the neuronal competence pathway permitted cytochrome c to activate caspases by inducing a marked reduction in XIAP levels in these neurons. Thus, the removal of XIAP inhibition appears both necessary and sufficient for cytochrome c to activate caspases in sympathetic neurons. These data identify a critical function of endogenous XIAP in regulating apoptosis in mammalian cells.
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spelling pubmed-21736932008-05-01 Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis Potts, Patrick Ryan Singh, Shweta Knezek, Malia Thompson, Craig B. Deshmukh, Mohanish J Cell Biol Article In sympathetic neurons, unlike most nonneuronal cells, growth factor withdrawal–induced apoptosis requires the development of competence in addition to cytochrome c release to activate caspases. Thus, although most nonneuronal cells die rapidly with cytosolic cytochrome c alone, sympathetic neurons are remarkably resistant unless they develop competence. We have identified endogenous X-linked inhibitor of apoptosis protein (XIAP) as the essential postcytochrome c regulator of caspase activation in these neurons. In contrast to wild-type neurons that are resistant to injection of cytochrome c, XIAP-deficient neurons died rapidly with cytosolic cytochrome c alone. Surprisingly, the release of endogenous Smac was not sufficient to overcome the XIAP resistance in sympathetic neurons. In contrast, the neuronal competence pathway permitted cytochrome c to activate caspases by inducing a marked reduction in XIAP levels in these neurons. Thus, the removal of XIAP inhibition appears both necessary and sufficient for cytochrome c to activate caspases in sympathetic neurons. These data identify a critical function of endogenous XIAP in regulating apoptosis in mammalian cells. The Rockefeller University Press 2003-11-24 /pmc/articles/PMC2173693/ /pubmed/14623868 http://dx.doi.org/10.1083/jcb.200307130 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Potts, Patrick Ryan
Singh, Shweta
Knezek, Malia
Thompson, Craig B.
Deshmukh, Mohanish
Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis
title Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis
title_full Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis
title_fullStr Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis
title_full_unstemmed Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis
title_short Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis
title_sort critical function of endogenous xiap in regulating caspase activation during sympathetic neuronal apoptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173693/
https://www.ncbi.nlm.nih.gov/pubmed/14623868
http://dx.doi.org/10.1083/jcb.200307130
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