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

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30 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)154-168
Number of pages15
JournalCell Death and Differentiation
Volume20
Issue number1
DOIs
Publication statusPublished - Jan 2013
Externally publishedYes

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Keywords

  • apoptosis
  • caspases
  • HuR
  • mRNA stability

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Von Roretz, C., Jin Lian, X., MacRi, A. M., Punjani, N., Clair, E., Drouin, O., Dormoy-Raclet, V., Ma, J. F., & Gallouzi, I. E. (2013). Apoptotic-induced cleavage shifts HuR from being a promoter of survival to an activator of caspase-mediated apoptosis. Cell Death and Differentiation, 20(1), 154-168. https://doi.org/10.1038/cdd.2012.111