Transcriptional Regulation by Wild-Type and Cancer-Related Mutant Forms of p53.
TP53 missense mutations produce a mutant p53 protein that cannot activate the p53 tumor suppressive transcriptional response, which is the primary selective pressure for TP53 mutation. Specific codons of TP53, termed hotspot mutants, are mutated at elevated frequency. Hotspot forms of mutant p53 possess oncogenic properties in addition to being deficient in tumor suppression. Such p53 mutants accumulate to high levels in the cells they inhabit, causing transcriptional alterations that produce pro-oncogenic activities, such as increased pro-growth signaling, invasiveness, and metastases. These forms of mutant p53 very likely use features of wild-type p53, such as interactions with the transcriptional machinery, to produce oncogenic effects. In this review, we discuss commonalities between wild-type and mutant p53 proteins with an emphasis on transcriptional processes.
Department of Biological Sciences, Columbia University, New York, New York 10027.
Neil T
NT
Pfister
Department of Biological Sciences, Columbia University, New York, New York 10027.
Carol
C
Prives
D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D020125:Mutation, Missense; D009369:Neoplasms / Q000235:genetics*; D015398:Signal Transduction; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
D016159:Tumor Suppressor Protein p53