Dataset Information

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

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.

SUBMITTER: Mooney SM

PROVIDER: S-EPMC2945537 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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

Mooney Steven M SM Goel Apollina A D'Assoro Antonino B AB Salisbury Jeffrey L JL Janknecht Ralf R

The Journal of biological chemistry 20100727 40

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 a ...[more]

PMID: 20663877

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Project description:BACKGROUND: The Oncominedatabase is an online collection of microarrays from various sources, usually cancer-related, and contains many "multi-arrays" (collections of analyzed microarrays, in a single study). As there are often many hundreds of tumour samples/microarrays within a single multi-array results from coexpressed genes can be analyzed, and are fully searchable. This gives a potentially significant list of coexpressed genes, which is important to define pathways in which the gene of interest is involved. However, to increase the likelihood of revealing truly significant coexpressed genes we have analyzed their frequency of occurrence over multiple studies (meta-analysis), greatly increasing the significance of results compared to those of a single study. RESULTS: We have used the DEAD-box proteins p68(Ddx5) and p72(Ddx17) as models for this coexpression frequency analysis as there are defined functions for these proteins in splicing and transcription (known functions which we could use as a basis for quality control). Furthermore, as these proteins are highly similar, interact together, and may be to some degree functionally redundant, we then analyzed the overlap between coexpressed genes of p68 and p72. This final analysis gave us a highly significant list of coexpressed genes, clustering mainly in splicing and transcription (recapitulating their published roles), but also revealing new pathways such as cytoskeleton remodelling and protein folding. We have further tested a predicted pathway partner, RNA helicase A(Dhx9) in a reciprocal meta-analysis that identified p68 and p72 as being coexpressed, and further show a direct interaction of Dhx9 with p68 and p72, attesting to the predictive nature of this technique. CONCLUSION: In summary we have extended the capabilities of Oncomineby analyzing the frequency of coexpressed genes over multiple studies, and furthermore assessing the overlap with a known pathway partner (in this case p68 with p72). We have shown our predictions corroborate previously published studies on p68 and p72, and that novel predictions can be easily tested. These techniques are widely applicable and should increase the quality of data from future meta-analysis studies.

Dataset Information

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

Publications

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

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