Gain-of-function mutations in the tumor suppressor gene p53.
The tumor suppressor protein p53 is a multifunctional transcription factor involved in the control of cell cycle progression, DNA integrity, and cell survival. p53 is mutated in half of all tumors and has a wide spectrum of mutation types. p53 mutants show different degrees of dominance over coexpressed wild-type p53, and loss of the wild-type p53 allele has been observed frequently. Several p53 mutants can exert oncogenic functions beyond their negative domination over the wild-type p53 tumor suppressor functions. These so-called gain-of-function effects, such as enhancement of tumorigenicity and therapy resistance, were investigated in p53-null cells. The possible mechanisms by which p53 mutants exert their gain-of-function effects are reviewed. The existence of functional gains of certain p53 mutants has important ramifications for tumor prognosis and cancer therapies.
van Oijen
M G
MG
Department of Pathology, University Medical Center Utrecht, The Netherlands.
Slootweg
P J
PJ
D000483:Alleles; D000818:Animals; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D017433:Protein Structure, Secondary; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000502:physiology
D016159:Tumor Suppressor Protein p53