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 Eddine Gallouzi

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

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. © The Rockefeller University Press.
Original languageEnglish (US)
Pages (from-to)113-127
Number of pages15
JournalJournal of Cell Biology
Volume180
Issue number1
DOIs
StatePublished - Jan 14 2008
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2022-09-13

ASJC Scopus subject areas

  • Cell Biology

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