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RNA-binding proteins implicated in the hypoxic response.

Abstract
In cells responding to low oxygen levels, gene expression patterns are strongly influenced by post-transcriptional processes. RNA-binding proteins (RBPs) are pivotal regulators of gene expression in response to numerous stresses, including hypoxia. Here, we review the RBPs that modulate mRNA turnover and translation in response to hypoxic challenge. The RBPs HuR (human antigen R) and PTB (polypyrimidine tract-binding protein) associate with mRNAs encoding hypoxia-response proteins such as HIF-1alpha and VEGF mRNAs, enhance their expression after hypoxia and play a major role in establishing hypoxic gene expression patterns. Additional RBPs such as iron-response element-binding proteins (IRPs), cytoplasmic polyadenylation-element-binding proteins (CPEBs) and several heterogeneous nuclear ribonucleoproteins (hnRNPs) also bind to hypoxia-regulated transcripts and modulate the levels of the encoded proteins. We discuss the efficient regulation of hypoxic gene expression by RBPs and the mounting interest in targeting hypoxia-regulatory RBPs in diseases with aberrant hypoxic responses.
AuthorsKiyoshi Masuda, Kotb Abdelmohsen, Myriam Gorospe
JournalJournal of cellular and molecular medicine (J Cell Mol Med) Vol. 13 Issue 9A Pg. 2759-69 (Sep 2009) ISSN: 1582-4934 [Electronic] England
PMID19583805 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Review)
Chemical References
  • Antigens, Surface
  • ELAV Proteins
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • RNA-Binding Proteins
Topics
  • Animals
  • Antigens, Surface (metabolism)
  • Cell Hypoxia (physiology)
  • ELAV Proteins
  • ELAV-Like Protein 1
  • Gene Expression Regulation
  • Humans
  • RNA-Binding Proteins (metabolism)

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