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

Kevin M. Wright, Michael W. Linhoff, Patrick Ryan Potts, Mohanish Deshmukh

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)303-313
Number of pages11
JournalJournal of Cell Biology
Volume167
Issue number2
DOIs
StatePublished - Oct 25 2004

Fingerprint

Apoptosomes
Inhibitor of Apoptosis Proteins
Apoptosis
PC12 Cells
Caspases
Cytochromes c
Pheochromocytoma
Cell Differentiation

ASJC Scopus subject areas

  • Cell Biology

Cite this

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.

In: Journal of Cell Biology, Vol. 167, No. 2, 25.10.2004, p. 303-313.

Research output: Contribution to journalArticle

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. In: Journal of Cell Biology. 2004 ; Vol. 167, No. 2. pp. 303-313.
@article{7bc53942840b4b96817e7915886c97c9,
title = "Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis",
abstract = "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 na{\"i}ve 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.",
author = "Wright, {Kevin M.} and Linhoff, {Michael W.} and Potts, {Patrick Ryan} and Mohanish Deshmukh",
year = "2004",
month = "10",
day = "25",
doi = "10.1083/jcb.200406073",
language = "English (US)",
volume = "167",
pages = "303--313",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "2",

}

TY - JOUR

T1 - Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis

AU - Wright, Kevin M.

AU - Linhoff, Michael W.

AU - Potts, Patrick Ryan

AU - Deshmukh, Mohanish

PY - 2004/10/25

Y1 - 2004/10/25

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=7244245454&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7244245454&partnerID=8YFLogxK

U2 - 10.1083/jcb.200406073

DO - 10.1083/jcb.200406073

M3 - Article

C2 - 15504912

AN - SCOPUS:7244245454

VL - 167

SP - 303

EP - 313

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 2

ER -