Human homologue of yeast Rad23 protein A interacts with p300/cyclic AMP-responsive element binding (CREB)-binding protein to down-regulate transcriptional activity of p53.
The tumor suppressor protein p53 regulates various cellular responses to DNA damage and plays a significant role in DNA repair. The nuclear p300/cyclic AMP-responsive element binding (CREB)-binding protein (CBP) proteins act as coactivators in supporting the transcription function of p53. We examined the role of the human homologue of yeast Rad23 protein A (hHR23A), one of the two human homologues of the Saccharomyces cerevisiae nucleotide excision repair gene product Rad23, in the p300/CBP-associated regulation of p53 activity. Overexpression of wild-type hHR23A inhibits the p53 transcriptional activity and results in a decreased steady-state protein level of cellular p53. The inhibitory effect of hHR23A can be overcome by the concomitant expression of p300, CBP, and p300 segments harboring C/H1 domain and neutralized by the coexpression of HIV accessory protein Vpr, which binds COOH terminus of hHR23A/B. Additionally, hHR23A was shown to interact in vitro and in vivo with p300 segments harboring C/H1 domain. These studies provide evidence for the involvement of hHR23A in the regulation of p53 activity through p300/CBP. Although the precise direct role of hHR23 proteins in regulation of p53 and DNA repair remains to be elucidated, our data suggest that the interaction between hHR23A and p300/CBP has important implications in cross-talk between the p53 pathway and DNA repair.
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Department of Radiology Ohio State University, Columbus 43210, USA.
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D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D050881:E1A-Associated p300 Protein; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology; D051736:Proto-Oncogene Proteins c-mdm2; D015534:Trans-Activators / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; C086985:RAD23A protein, human; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; D045643:DNA Repair Enzymes