The p53 response during DNA damage: impact of transcriptional cofactors.
Defects in the DNA damage response pathways can lead to tumour development. The tumour suppressor p53 is a key player in the DNA damage response, and the precise regulation of p53 is critical for the suppression of tumorigenesis. DNA damage induces the activity of p53, via damage sensors such as ATM (ataxia telangiectasia mutated) and ATR (ataxia telangiectasia-related), which leads to the transcriptional regulation of a variety of genes involved in cell cycle control and apoptosis. p53 is therefore tightly controlled, and its activity is regulated at a multiplicity of levels. An increasing array of cofactors are now known to influence p53 activity. Here we will discuss several of the cofactors that impact on p53 activity, specifically those involved in the function of the two novel p53 cofactors JMY (junction-mediating and regulatory protein) and Strap (serine/threonine-kinase-receptor-associated protein).
Coutts
Amanda S
AS
Laboratory of Cancer Biology, Division of Medical Sciences, University of Oxford, Oxford OX3 9DU, UK.
La Thangue
Nicholas
N
D050882:CREB-Binding Protein / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D016158:Genes, p53; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D016601:RNA-Binding Proteins; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D002843:Chromatin; C121977:JMY protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C403447:STRAP protein, human; C495901:TP53 protein, human; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2