Mdm2 widens its repertoire.
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.
Coutts
Amanda S
AS
Laboratory of Cancer Biology, Division of Medical Sciences, University of Oxford, Oxford, UK.
La Thangue
Nicholas B
NB
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
C121977:JMY protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2; D046988:Proteasome Endopeptidase Complex