The central acidic domain of MDM2 is critical in inhibition of retinoblastoma-mediated suppression of E2F and cell growth

Sdek, P., Ying, H. Q., Zheng, H. W., Margulis, A., Tang, X. R., Tian, K., Xiao, Z. X. J. (December 2004) The central acidic domain of MDM2 is critical in inhibition of retinoblastoma-mediated suppression of E2F and cell growth. Journal of Biological Chemistry, 279 (51). pp. 53317-53322. ISSN 0021-9258

URL: http://www.ncbi.nlm.nih.gov/pubmed/15485814
DOI: 10.1074/jbc.M406062200

Abstract

Retinoblastoma (Rb) protein is a paradigm of tumor suppressors. Inactivation of Rb plays a critical role in the development of human malignancies. MDM2, an oncogene frequently found amplified and overexpressed in a variety of human tumors and cancers, directly interacts and inhibits the p53 tumor suppressor protein. In addition, MDM2 has been shown to stimulate E2F transactivation activity and promote S-phase entry independent of p53, yet the mechanism of which is still not fully understood. In this study, we demonstrate that MDM2 specifically binds to Rb C-pocket and that the central acidic domain of MDM2 is essential for Rb interaction. In addition, we show that overexpression of MDM2 reduces Rb-E2F complexes in vivo. Moreover, the ectopic expression of the wild type MDM2, but not mutant MDM2 defective in Rb interaction, stimulates E2F transactivation activity and inhibits Rb growth suppression function. Taken together, these results suggest that MDM2-mediated inhibition of Rb likely contributes to MDM2 oncogenic activity.

Item Type: Paper
Uncontrolled Keywords: TRANSCRIPTION FACTOR ONCOPROTEIN MDM2 TUMOR-SUPPRESSOR GENE-PRODUCT RING FINGER UBIQUITIN LIGASE BINDING DOMAIN P53 PROTEIN RB Biochemistry & Molecular Biology
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > tumor suppressor
CSHL Authors:
Communities: CSHL labs > Zheng lab
Depositing User: Matt Covey
Date: December 2004
Date Deposited: 22 Aug 2014 15:36
Last Modified: 22 Aug 2014 15:36
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30709

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