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RB18A enhances expression of mutant p53 protein in human cells
Author(s) -
Lottin-Divoux Séverine,
Barel Monique,
Frade Raymond
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.03.026
Subject(s) - mutant , microbiology and biotechnology , mdm2 , downregulation and upregulation , suppressor , transcription (linguistics) , transcription factor , chemistry , p53 protein , biology , biochemistry , gene , linguistics , philosophy
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.