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Pleiotropic effects of p300-mediated acetylation on p68 and p72 RNA helicase.

Authors
  • Mooney, Steven M
  • Goel, Apollina
  • D'Assoro, Antonino B
  • Salisbury, Jeffrey L
  • Janknecht, Ralf
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry and Molecular Biology
Publication Date
Oct 01, 2010
Volume
285
Issue
40
Pages
30443–30452
Identifiers
DOI: 10.1074/jbc.M110.143792
PMID: 20663877
Source
Medline
License
Unknown

Abstract

Here, we demonstrate that p68 (DDX5) and p72 (DDX17), two homologous RNA helicases and transcriptional cofactors, are substrates for the acetyltransferase p300 in vitro and in vivo. Mutation of acetylation sites affected the binding of p68/p72 to histone deacetylases, but not to p300 or estrogen receptor. Acetylation additionally increased the stability of p68 and p72 RNA helicase and stimulated their ability to coactivate the estrogen receptor, thereby potentially contributing to its aberrant activation in breast tumors. Also, acetylation of p72, but not of p68 RNA helicase, enhanced p53-dependent activation of the MDM2 promoter, pointing at another mechanism of how p72 acetylation may facilitate carcinogenesis by boosting the negative p53-MDM2 feedback loop. Furthermore, blocking p72 acetylation caused cell cycle arrest and apoptosis, revealing an essential role for p72 acetylation. In conclusion, our report has identified for the first time that acetylation modulates RNA helicases and provides multiple mechanisms how acetylation of p68 and p72 may affect normal and tumor cells.

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