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The p53 tumor suppressor protein is a DNA damage responsive transcription factor that affects diverse cellular processes which include transcription, DNA synthesis and repair, cell cycle arrest, senescence and apoptosis. The Mdm2 oncoprotein is a primary regulator of p53, mediating p53 control via ubiquitin-dependent proteasomal degradation. During DNA damage, the interaction between p53 and Mdm2 is reduced, which allows p53 levels to accumulate. p53 activity is tightly controlled and regulated at a multiplicity of levels, and the importance of co-factors that influence p53 activity is becoming increasingly evident. Recent studies have highlighted the role of Mdm2 in the control of p53 co-factors. Thus, Mdm2 targets JMY, a p53 co-factor, for ubiquitin-dependent Mdm2 targets JMY, a p53 co-factor, for ubiquitin-dependent proteasomal degradation and in doing so overcomes the ability of JMY to augment the p53 response. These results define a new functional relationship between control of p53 activity and Mdm2, and suggest that transcription co-factors which facilitate the p53 response are important targets through which Mdm2 mediates its oncogenic activity.

Original publication

DOI

10.4161/cc.6.7.4086

Type

Journal article

Journal

Cell Cycle

Publication Date

01/04/2007

Volume

6

Pages

827 - 829

Keywords

Animals, Cell Transformation, Neoplastic, DNA Damage, Gene Expression Regulation, Neoplastic, Humans, Nuclear Proteins, Proteasome Endopeptidase Complex, Proto-Oncogene Proteins c-mdm2, Regulatory Elements, Transcriptional, Trans-Activators, Tumor Suppressor Protein p53