RB18A regulates p53-dependent apoptosis.
We previously demonstrated that RB18A, a member of TRAP220/DRIP205/PBP family, in vivo acted as a cofactor of transcription by differently regulating p53wt transactivating activity on physiological promoters. Using p53-negative cells transfected with different constructs, we herein demonstrated that RB18A down-regulated p53wt-dependent apoptosis. This biological regulation was due to a specific diminution of p53wt protein level, as level of p53mut and GAPDH proteins was not modified. This p53wt diminution was dependent on proteasome activity, as inhibited by MG-132 inhibitor. This specific p53wt degradation was correlated with an increase in expression of MDM2, which promoted p53wt degradation into proteasome. RB18A up-regulated MDM2 expression by activating MDM2 promoter, even in absence of p53wt. Altogether, these data emphasized that RB18A could regulate p53wt function not only by direct interaction between both proteins, but also by up-regulating promoter activity of MDM2, a p53-regulating partner.
Frade
Raymond
R
Immunochimie des Régulations Cellulaires et des Interactions Virales, INSERM U.354, Centre INSERM, Hôpital Saint-Antoine, 75012, Paris, France. frade354@easynet.fr
Balbo
Michelle
M
Barel
Monique
M
D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D018236:Carcinoma, Embryonal / Q000473:pathology; D002352:Carrier Proteins / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D016158:Genes, p53; D006801:Humans; D020014:K562 Cells / Q000166:cytology / Q000378:metabolism; D008175:Lung Neoplasms / Q000473:pathology; D056913:Mediator Complex Subunit 1; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D051736:Proto-Oncogene Proteins c-mdm2; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000502:physiology*
D002352:Carrier Proteins; D018076:DNA, Complementary; C538855:MED1 protein, human; D056913:Mediator Complex Subunit 1; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2