Mutant p53: one name, many proteins.
There is now strong evidence that mutation not only abrogates p53 tumor-suppressive functions, but in some instances can also endow mutant proteins with novel activities. Such neomorphic p53 proteins are capable of dramatically altering tumor cell behavior, primarily through their interactions with other cellular proteins and regulation of cancer cell transcriptional programs. Different missense mutations in p53 may confer unique activities and thereby offer insight into the mutagenic events that drive tumor progression. Here we review mechanisms by which mutant p53 exerts its cellular effects, with a particular focus on the burgeoning mutant p53 transcriptome, and discuss the biological and clinical consequences of mutant p53 gain of function.
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
William A
WA
Freed-Pastor
Carol
C
Prives
D006801:Humans; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D050505:Mutant Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53