RB18A enhances expression of mutant p53 protein in human cells.
RB18A (TRAP220/DRIP205) is a cofactor of transcription. We herein demonstrated that RB18A downregulated p53 and upregulated MDM2 promoters. These RB18A regulations, not modified by p53wt expression, were inhibited by mutant p53 (p53mut) expression, which directly interacts with RB18A D5 domain. In addition, RB18A via its D4 domain, also interacts directly and specifically with MDM2 protein inhibiting p53mut degradation. Altogether, these mechanisms contribute to maintain a high level of p53mut expression in tumor proliferating cells. Therefore, RB18A plays a central role to control p53wt and p53mut protein content and functions in cells through a loop of regulation, which involves MDM2.
Lottin-Divoux
Séverine
S
INSERM U.672 (ex U.354), Immunochimie des Régulations Cellulaires et des Interactions Virales, Bâtiment G8, Génopole d'Evry, France.
Barel
Monique
M
Frade
Raymond
R
D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D056913:Mediator Complex Subunit 1; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
C538855:MED1 protein, human; D056913:Mediator Complex Subunit 1; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2