The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor.
The DEAD box RNA helicase, p68, has been implicated in various cellular processes and has been shown to possess transcriptional coactivator function. Here, we show that p68 potently synergises with the p53 tumour suppressor protein to stimulate transcription from p53-dependent promoters and that endogenous p68 and p53 co-immunoprecipitate from nuclear extracts. Strikingly, RNAi suppression of p68 inhibits p53 target gene expression in response to DNA damage, as well as p53-dependent apoptosis, but does not influence p53 stabilisation or expression of non-p53-responsive genes. We also show, by chromatin immunoprecipitation, that p68 is recruited to the p21 promoter in a p53-dependent manner, consistent with a role in promoting transcriptional initiation. Interestingly, p68 knock-down does not significantly affect NF-kappaB activation, suggesting that the stimulation of p53 transcriptional activity is not due to a general transcription effect. This study represents the first report of the involvement of an RNA helicase in the p53 response, and highlights a novel mechanism by which p68 may act as a tumour cosuppressor in governing p53 transcriptional activity.
Bates
Gaynor J
GJ
Department of Molecular & Cellular Pathology, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK.
Nicol
Samantha M
SM
Wilson
Brian J
BJ
Jacobs
Anne-Marie F
AM
Bourdon
Jean-Christophe
JC
Wardrop
Julie
J
Gregory
David J
DJ
Lane
David P
DP
Perkins
Neil D
ND
Fuller-Pace
Frances V
FV
D017209:Apoptosis; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D053487:DEAD-box RNA Helicases; D004249:DNA Damage; D016158:Genes, p53; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D020365:RNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016328:NF-kappa B; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases; C506749:Ddx5 protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)