Mutant p53 proteins: between loss and gain of function.
Cancer might result from both the aberrant activation of genes, whose physiological tuning is essential for the life of a normal cell, and the inactivation of tumor suppressor genes, whose main job is to preserve the integrity of cell genome. Among the latter, p53 is considered a key tumor suppressor gene that is inactivated mainly by missense mutations in half of human cancers. It is becoming increasingly clear that the resulting mutant p53 proteins gain oncogenic properties favoring the insurgence, the maintenance, and the spreading of malignant tumors. In this review, we mainly discuss the molecular mechanisms underlying gain of function of human tumor-derived p53 mutants, their impact on the chemoresistance and the prognosis of human tumors, with a special focus on head and neck cancers, and the perspectives of treating tumors through the manipulation of mutant p53 proteins.
Strano
Sabrina
S
Department of Experimental Oncology, Regina Elena Cancer Institute, 00158 Rome, Italy.
Dell'Orso
Stefania
S
Mongiovi
Adriana Maria
AM
Monti
Olimpia
O
Lapi
Eleonora
E
Di Agostino
Silvia
S
Fontemaggi
Giulia
G
Blandino
Giovanni
G
D000256:Adenoviridae / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000628:therapy; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000628:therapy; D006801:Humans; D009154:Mutation; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology*; D014765:Viral Vaccines
D016159:Tumor Suppressor Protein p53; D014765:Viral Vaccines; C464532:dl1520