RB18A enhances expression of mutant p53 protein in human cells

Séverine Lottin-Divoux; Monique Barel; Raymond Frade

doi:10.1016/j.febslet.2005.03.026

RB18A enhances expression of mutant p53 protein in human cells

FEBS Lett. 2005 Apr 25;579(11):2323-6. doi: 10.1016/j.febslet.2005.03.026.

Authors

Séverine Lottin-Divoux¹, Monique Barel, Raymond Frade

Affiliation

¹ INSERM U.672 (ex U.354), Immunochimie des Régulations Cellulaires et des Interactions Virales, Bâtiment G8, Génopole d'Evry, France.

PMID: 15848166
DOI: 10.1016/j.febslet.2005.03.026

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line
Down-Regulation
Humans
Mediator Complex Subunit 1
Mutation / genetics
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Promoter Regions, Genetic / genetics
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-mdm2
Transcription Factors / genetics
Transcription Factors / metabolism*
Tumor Suppressor Protein p53 / genetics*
Tumor Suppressor Protein p53 / metabolism
Up-Regulation*

Substances

MED1 protein, human
Mediator Complex Subunit 1
Nuclear Proteins
Proto-Oncogene Proteins
Transcription Factors
Tumor Suppressor Protein p53
MDM2 protein, human
Proto-Oncogene Proteins c-mdm2