Apoptotic-induced cleavage shifts HuR from being a promoter of survival to an activator of caspase-mediated apoptosis

C. Von Roretz, X. Jin Lian, A. M. MacRi, N. Punjani, E. Clair, O. Drouin, V. Dormoy-Raclet, J. F. Ma, I. E. Gallouzi

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Little is known about the cellular mechanisms modulating the shift in balance from a state of survival to cell death by caspase-mediated apoptosis in response to a lethal stress. Here we show that the RNA-binding protein HuR has an important function in mediating this switch. During caspase-mediated apoptosis, HuR is cleaved to generate two cleavage products (CPs). Our data demonstrate that the cleavage of HuR switches its function from being a prosurvival factor under normal conditions to becoming a promoter of apoptosis in response to a lethal stress. In the absence of an apoptotic stimuli, HuR associates with and promotes the expression of caspase-9 and prothymosin (ProT) mRNAs, and pro-and antiapoptotic factors, respectively, both of which have been characterized as important players in determining cell fate. During the early steps of caspase-mediated apoptosis, however, the level of caspase-9 protein increases, while ProT remains unchanged. Under these conditions, the two HuR-CPs selectively bind to and stabilize caspase-9 mRNA, but do not bind to ProT. Hence, taken together, our data show that by maintaining a threshold of expression of proapoptotic factors such as caspase-9 in response to a lethal stress, the HuR-CPs help a cell to switch from resisting death to undergoing apoptosis. © 2013 Macmillan Publishers Limited All rights reserved.
Original languageEnglish (US)
Pages (from-to)154-168
Number of pages15
JournalCell Death and Differentiation
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Bibliographical note

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

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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