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Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis

Despite the potential of the inhibitor of apoptosis proteins (IAPs) to block cytochrome c–dependent caspase activation, the critical function of IAPs in regulating mammalian apoptosis remains unclear. We report that the ability of endogenous IAPs to effectively regulate caspase activation depends on...

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Detalles Bibliográficos
Autores principales: Wright, Kevin M., Linhoff, Michael W., Potts, Patrick Ryan, Deshmukh, Mohanish
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172554/
https://www.ncbi.nlm.nih.gov/pubmed/15504912
http://dx.doi.org/10.1083/jcb.200406073
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author Wright, Kevin M.
Linhoff, Michael W.
Potts, Patrick Ryan
Deshmukh, Mohanish
author_facet Wright, Kevin M.
Linhoff, Michael W.
Potts, Patrick Ryan
Deshmukh, Mohanish
author_sort Wright, Kevin M.
collection PubMed
description Despite the potential of the inhibitor of apoptosis proteins (IAPs) to block cytochrome c–dependent caspase activation, the critical function of IAPs in regulating mammalian apoptosis remains unclear. We report that the ability of endogenous IAPs to effectively regulate caspase activation depends on the differentiation state of the cell. Despite being expressed at equivalent levels, endogenous IAPs afforded no protection against cytochrome c–induced apoptosis in naïve pheochromocytoma (PC12) cells, but were remarkably effective in doing so in neuronally differentiated cells. Neuronal differentiation was also accompanied with a marked reduction in Apaf-1, resulting in a significant decrease in apoptosome activity. Importantly, this decrease in Apaf-1 protein was directly linked to the increased ability of IAPs to stringently regulate apoptosis in neuronally differentiated PC12 and primary cells. These data illustrate specifically how the apoptotic pathway acquires increased regulation with cellular differentiation, and are the first to show that IAP function and apoptosome activity are coupled in cells.
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spelling pubmed-21725542008-03-05 Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis Wright, Kevin M. Linhoff, Michael W. Potts, Patrick Ryan Deshmukh, Mohanish J Cell Biol Research Articles Despite the potential of the inhibitor of apoptosis proteins (IAPs) to block cytochrome c–dependent caspase activation, the critical function of IAPs in regulating mammalian apoptosis remains unclear. We report that the ability of endogenous IAPs to effectively regulate caspase activation depends on the differentiation state of the cell. Despite being expressed at equivalent levels, endogenous IAPs afforded no protection against cytochrome c–induced apoptosis in naïve pheochromocytoma (PC12) cells, but were remarkably effective in doing so in neuronally differentiated cells. Neuronal differentiation was also accompanied with a marked reduction in Apaf-1, resulting in a significant decrease in apoptosome activity. Importantly, this decrease in Apaf-1 protein was directly linked to the increased ability of IAPs to stringently regulate apoptosis in neuronally differentiated PC12 and primary cells. These data illustrate specifically how the apoptotic pathway acquires increased regulation with cellular differentiation, and are the first to show that IAP function and apoptosome activity are coupled in cells. The Rockefeller University Press 2004-10-25 /pmc/articles/PMC2172554/ /pubmed/15504912 http://dx.doi.org/10.1083/jcb.200406073 Text en Copyright © 2004, 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 Research Articles
Wright, Kevin M.
Linhoff, Michael W.
Potts, Patrick Ryan
Deshmukh, Mohanish
Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis
title Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis
title_full Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis
title_fullStr Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis
title_full_unstemmed Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis
title_short Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis
title_sort decreased apoptosome activity with neuronal differentiation sets the threshold for strict iap regulation of apoptosis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172554/
https://www.ncbi.nlm.nih.gov/pubmed/15504912
http://dx.doi.org/10.1083/jcb.200406073
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