MDM2 inhibits PCAF (p300/CREB-binding protein-associated factor)-mediated p53 acetylation.
Our previous study shows that MDM2, a negative feedback regulator of the tumor suppressor p53, inhibits p300-mediated p53 acetylation. Because PCAF (p300/CREB-binding protein-associated factor) also acetylates and activates p53 after DNA damage, in this study we have examined the effect of MDM2 on PCAF-mediated p53 acetylation. We have found that MDM2 inhibited p53 acetylation by PCAF in vitro. In addition, when overexpressed, MDM2 inhibited PCAF-mediated p53 acetylation in cells. MDM2 interacted with PCAF both in vitro and in cells, as assessed using GST fusion protein interaction and immunoprecipitation assays, respectively. Consistent with the above results, MDM2 significantly repressed the activation of p53 transcriptional activity by PCAF without apparently affecting the level of p53. In addition, MDM2 co-resided with p53 at the p53-responsive mdm2 and p21(waf1/cip1) promoters, inhibiting expression of the endogenous p21(waf1/cip1). These results demonstrate that MDM2 can inhibit PCAF-mediated p53 acetylation and activation.
Jin
Yetao
Y
Department of Biochemistry and Molecular Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA.
Zeng
Shelya X
SX
Dai
Mu-Shui
MS
Yang
Xiang-Jiao
XJ
Lu
Hua
H
D000107:Acetylation; D000123:Acetyltransferases / Q000037:antagonists & inhibitors*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004249:DNA Damage; D051548:Histone Acetyltransferases; D006801:Humans; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051736:Proto-Oncogene Proteins c-mdm2; D014157:Transcription Factors; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D051548:Histone Acetyltransferases; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C493956:CDKN1A protein, human; C497206:MDM2 protein, human