Growth factor dependent regulation of centrosome function and genomic instability by HuR

Biomolecules. 2015 Mar 20;5(1):263-81. doi: 10.3390/biom5010263.

Abstract

The mRNA binding protein HuR is over expressed in cancer cells and contributes to disease progression through post-transcriptional regulation of mRNA. The regulation of HuR and how this relates to glioma is the focus of this report. SRC and c-Abl kinases regulate HuR sub-cellular trafficking and influence accumulation in the pericentriolar matrix (PCM) via a growth factor dependent signaling mechanism. Growth factor stimulation of glioma cell lines results in the associate of HuR with the PCM and amplification of centrosome number. This process is regulated by tyrosine phosphorylation of HuR and is abolished by mutating tyrosine residues. HuR is overexpressed in tumor samples from patients with glioblastoma and associated with a reduced survival. These findings suggest HuR plays a significant role in centrosome amplification and genomic instability, which contributes to a worse disease outcome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Centrosome / drug effects*
  • Centrosome / metabolism*
  • ELAV Proteins / chemistry
  • ELAV Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genomic Instability / drug effects*
  • Glioma / pathology
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-abl / metabolism
  • Tyrosine / metabolism
  • src-Family Kinases / metabolism

Substances

  • ELAV Proteins
  • Intercellular Signaling Peptides and Proteins
  • Tyrosine
  • Proto-Oncogene Proteins c-abl
  • src-Family Kinases