p53 ubiquitination by Mdm2: a never ending tail?
p53 function is of critical importance in suppressing human cancer formation, highlighted by the fact that the majority of human tumors harbor compromised p53 activity. In normal cells, p53 is held at low levels in a latent form and cellular stress results in the rapid stabilization of p53. Mdm2 mediates ubiquitin-dependent degradation of p53 which plays a key role in maintaining cellular p53 levels. Ubiquitination was, until recently, considered a straightforward system involved in p53 degradation, but recent work has demonstrated how ubiquitination can alter p53 activity, not stability. In this review we summarize current understanding on p53 ubiquitination by Mdm2 with a particular focus on how the balance between protein levels and other post-translational modifications will direct the p53 response.
Coutts
Amanda S
AS
Medical Sciences Division, Department of Clinical Pharmacology, University of Oxford, Oxford OX3 7DQ, UK.
Adams
Cassandra J
CJ
La Thangue
Nicholas B
NB
D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D054875:Ubiquitination
D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2