Role of the RNA-binding protein HuR in apoptosis and apoptosome function

Yuki Kuwano, Imed Gallouzi, Myriam Gorospe

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Citations (Scopus)

Abstract

In response to damaging agents, cells alter gene expression patterns through transcriptional and post-transcriptional mechanisms. Among the major post-transcriptional regulators of gene expression is the RNA-binding protein HuR, which stabilizes or regulates the translation of target mRNAs. HuR function is modulated by stress-causing agents including oxidants, genotoxins, inflammatory stimuli, and nutrient deprivation. By influencing the expression of target mRNAs and protein ligands, HuR has been shown to influence cellular function in multiple ways, including by modulating apoptosis. In this chapter, we describe the dual influence of HuR on programmed cell death. In response to moderate, repairable stress, HuR was found to bind numerous mRNAs encoding inhibitors of apoptosis and apoptosome activity (e.g., prothymosin α, Bcl-2, Mcl-1, SIRT1, cyclins, HIF-1α, p21) and elevated their expression. In several instances, these proteins were demonstrated effectors of HuR pro-survival actions. By contrast, in response to irreparable stress, HuR was reported to promote apoptosis through its association with protein ligand pp32/PHAPI, a potent activator of the apoptosome. HuR can also modulate the expression of pro-apoptotic proteins such as p53, c-myc, and p27Kip1, but their involvement in HuR-triggered apoptosis remains to be studied. In sum, the association of HuR with specific mRNAs and proteins can either promote or inhibit cell death. We describe how these seemingly antagonistic functions of HuR on apoptosis are regulated and we discuss how HuR function is integrated in the overall homeostatic program of the cell.

Original languageEnglish
Title of host publicationApoptosome: An Up-and-coming Therapeutical Tool
PublisherSpringer Netherlands
Pages203-220
Number of pages18
ISBN (Electronic)9789048134151
ISBN (Print)9789048134144
DOIs
Publication statusPublished - 2010
Externally publishedYes

Fingerprint

Apoptosomes
RNA-Binding Proteins
Apoptosis
Messenger RNA
Cell Death
Ligands
Gene Expression
Apoptosis Regulatory Proteins
Proteins
Cyclins
Mutagens
Protein Biosynthesis
Regulator Genes
Oxidants
Food

Keywords

  • mRNA stability
  • Ribonucleoprotein complex
  • Translational control post-transcriptional gene regulation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kuwano, Y., Gallouzi, I., & Gorospe, M. (2010). Role of the RNA-binding protein HuR in apoptosis and apoptosome function. In Apoptosome: An Up-and-coming Therapeutical Tool (pp. 203-220). Springer Netherlands. https://doi.org/10.1007/978-90-481-3415-1-10

Role of the RNA-binding protein HuR in apoptosis and apoptosome function. / Kuwano, Yuki; Gallouzi, Imed; Gorospe, Myriam.

Apoptosome: An Up-and-coming Therapeutical Tool. Springer Netherlands, 2010. p. 203-220.

Research output: Chapter in Book/Report/Conference proceedingChapter

Kuwano, Y, Gallouzi, I & Gorospe, M 2010, Role of the RNA-binding protein HuR in apoptosis and apoptosome function. in Apoptosome: An Up-and-coming Therapeutical Tool. Springer Netherlands, pp. 203-220. https://doi.org/10.1007/978-90-481-3415-1-10
Kuwano Y, Gallouzi I, Gorospe M. Role of the RNA-binding protein HuR in apoptosis and apoptosome function. In Apoptosome: An Up-and-coming Therapeutical Tool. Springer Netherlands. 2010. p. 203-220 https://doi.org/10.1007/978-90-481-3415-1-10
Kuwano, Yuki ; Gallouzi, Imed ; Gorospe, Myriam. / Role of the RNA-binding protein HuR in apoptosis and apoptosome function. Apoptosome: An Up-and-coming Therapeutical Tool. Springer Netherlands, 2010. pp. 203-220
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