Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis

Rachid Mazroui, Sergio Di Marco, Eveline Clair, Christopher Von Roretz, Scott A. Tenenbaum, Jack D. Keene, Maya Saleh, Imed Gallouzi

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

The RNA-binding protein HuR affects cell fate by regulating the stability and/or the translation of messenger RNAs that encode cell stress response proteins. In this study, we delineate a novel regulatory mechanism by which HuR contributes to stress-induced cell death. Upon lethal stress, HuR translocates into the cytoplasm by a mechanism involving its association with the apoptosome activator pp32/PHAP-I. Depleting the expression of pp32/PHAP-I by RNA interference reduces both HuR cytoplasmic accumulation and the efficiency of caspase activation. In the cytoplasm, HuR undergoes caspase-mediated cleavage at aspartate 226. This cleavage activity is significantly reduced in the absence of pp32/PHAP-I. Substituting aspartate 226 with an alanine creates a noncleavable isoform of HuR that, when over expressed, maintains its association with pp32/PHAP-I and delays the apoptotic response. Thus, we propose a model in which HuR association with pp32/PHAP-I and its caspase-mediated cleavage constitutes a regulatory step that contributes to an amplified apoptotic response.

Original languageEnglish
Pages (from-to)113-127
Number of pages15
JournalJournal of Cell Biology
Volume180
Issue number1
DOIs
Publication statusPublished - 14 Jan 2008
Externally publishedYes

Fingerprint

Caspases
Cytoplasm
Apoptosis
Aspartic Acid
Apoptosomes
RNA-Binding Proteins
Heat-Shock Proteins
RNA Interference
Alanine
Protein Isoforms
Cell Death
Messenger RNA

ASJC Scopus subject areas

  • Cell Biology

Cite this

Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis. / Mazroui, Rachid; Di Marco, Sergio; Clair, Eveline; Von Roretz, Christopher; Tenenbaum, Scott A.; Keene, Jack D.; Saleh, Maya; Gallouzi, Imed.

In: Journal of Cell Biology, Vol. 180, No. 1, 14.01.2008, p. 113-127.

Research output: Contribution to journalArticle

Mazroui, R, Di Marco, S, Clair, E, Von Roretz, C, Tenenbaum, SA, Keene, JD, Saleh, M & Gallouzi, I 2008, 'Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis', Journal of Cell Biology, vol. 180, no. 1, pp. 113-127. https://doi.org/10.1083/jcb.200709030
Mazroui R, Di Marco S, Clair E, Von Roretz C, Tenenbaum SA, Keene JD et al. Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis. Journal of Cell Biology. 2008 Jan 14;180(1):113-127. https://doi.org/10.1083/jcb.200709030
Mazroui, Rachid ; Di Marco, Sergio ; Clair, Eveline ; Von Roretz, Christopher ; Tenenbaum, Scott A. ; Keene, Jack D. ; Saleh, Maya ; Gallouzi, Imed. / Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis. In: Journal of Cell Biology. 2008 ; Vol. 180, No. 1. pp. 113-127.
@article{88fef9592fe04f3f9e92f1e017e26aa0,
title = "Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis",
abstract = "The RNA-binding protein HuR affects cell fate by regulating the stability and/or the translation of messenger RNAs that encode cell stress response proteins. In this study, we delineate a novel regulatory mechanism by which HuR contributes to stress-induced cell death. Upon lethal stress, HuR translocates into the cytoplasm by a mechanism involving its association with the apoptosome activator pp32/PHAP-I. Depleting the expression of pp32/PHAP-I by RNA interference reduces both HuR cytoplasmic accumulation and the efficiency of caspase activation. In the cytoplasm, HuR undergoes caspase-mediated cleavage at aspartate 226. This cleavage activity is significantly reduced in the absence of pp32/PHAP-I. Substituting aspartate 226 with an alanine creates a noncleavable isoform of HuR that, when over expressed, maintains its association with pp32/PHAP-I and delays the apoptotic response. Thus, we propose a model in which HuR association with pp32/PHAP-I and its caspase-mediated cleavage constitutes a regulatory step that contributes to an amplified apoptotic response.",
author = "Rachid Mazroui and {Di Marco}, Sergio and Eveline Clair and {Von Roretz}, Christopher and Tenenbaum, {Scott A.} and Keene, {Jack D.} and Maya Saleh and Imed Gallouzi",
year = "2008",
month = "1",
day = "14",
doi = "10.1083/jcb.200709030",
language = "English",
volume = "180",
pages = "113--127",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "1",

}

TY - JOUR

T1 - Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis

AU - Mazroui, Rachid

AU - Di Marco, Sergio

AU - Clair, Eveline

AU - Von Roretz, Christopher

AU - Tenenbaum, Scott A.

AU - Keene, Jack D.

AU - Saleh, Maya

AU - Gallouzi, Imed

PY - 2008/1/14

Y1 - 2008/1/14

N2 - The RNA-binding protein HuR affects cell fate by regulating the stability and/or the translation of messenger RNAs that encode cell stress response proteins. In this study, we delineate a novel regulatory mechanism by which HuR contributes to stress-induced cell death. Upon lethal stress, HuR translocates into the cytoplasm by a mechanism involving its association with the apoptosome activator pp32/PHAP-I. Depleting the expression of pp32/PHAP-I by RNA interference reduces both HuR cytoplasmic accumulation and the efficiency of caspase activation. In the cytoplasm, HuR undergoes caspase-mediated cleavage at aspartate 226. This cleavage activity is significantly reduced in the absence of pp32/PHAP-I. Substituting aspartate 226 with an alanine creates a noncleavable isoform of HuR that, when over expressed, maintains its association with pp32/PHAP-I and delays the apoptotic response. Thus, we propose a model in which HuR association with pp32/PHAP-I and its caspase-mediated cleavage constitutes a regulatory step that contributes to an amplified apoptotic response.

AB - The RNA-binding protein HuR affects cell fate by regulating the stability and/or the translation of messenger RNAs that encode cell stress response proteins. In this study, we delineate a novel regulatory mechanism by which HuR contributes to stress-induced cell death. Upon lethal stress, HuR translocates into the cytoplasm by a mechanism involving its association with the apoptosome activator pp32/PHAP-I. Depleting the expression of pp32/PHAP-I by RNA interference reduces both HuR cytoplasmic accumulation and the efficiency of caspase activation. In the cytoplasm, HuR undergoes caspase-mediated cleavage at aspartate 226. This cleavage activity is significantly reduced in the absence of pp32/PHAP-I. Substituting aspartate 226 with an alanine creates a noncleavable isoform of HuR that, when over expressed, maintains its association with pp32/PHAP-I and delays the apoptotic response. Thus, we propose a model in which HuR association with pp32/PHAP-I and its caspase-mediated cleavage constitutes a regulatory step that contributes to an amplified apoptotic response.

UR - http://www.scopus.com/inward/record.url?scp=38349047829&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38349047829&partnerID=8YFLogxK

U2 - 10.1083/jcb.200709030

DO - 10.1083/jcb.200709030

M3 - Article

VL - 180

SP - 113

EP - 127

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 1

ER -