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Gain-of-function mutations in the tumor suppressor gene p53 van Oijen MG; Slootweg PJClin Cancer Res 2000[Jun]; 6 (6): 2138-45The 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.|*Mutation[MESH]|Alleles[MESH]|Animals[MESH]|Genes, p53/*genetics[MESH]|Humans[MESH]|Loss of Heterozygosity[MESH]|Mice[MESH]|Models, Genetic[MESH]|Protein Structure, Secondary[MESH]|Tumor Suppressor Protein p53/*chemistry/physiology[MESH] |
