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- W2906965285 abstract "Gain-of-function (GOF), the most malicious oncogenic activity of a cancer-promoting protein, is well illustrated to three hotspot p53 mutations at R248, R175, and R273 with distinct molecular mechanisms. Yet, less is known about another hotspot p53 mutant, R249S (p53-R249S). p53-R249S is the sole hotspot mutation in hepatocellular carcinoma (HCC) that is highly associated with chronic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin B1 (AFB1). Its GOF is suggested by the facts that this mutant is associated with earlier onset of HCC and poorer prognosis of cancer patients and that its overexpression drives HCC proliferation and tumorigenesis. By contrast, simply knocking in this mutant in normal mice did not show apparent GOF activity. Hence, the GOF activity for p53-R249S and its underlying mechanisms have been elusive until recent findings offered some new insights. This review will discuss these findings as well as their clinical significance and implications for the development of a strategy to target multiple molecules as a therapy for p53-R249S-harboring HCC." @default.
- W2906965285 created "2019-01-11" @default.
- W2906965285 creator A5004117648 @default.
- W2906965285 creator A5043299001 @default.
- W2906965285 creator A5050868515 @default.
- W2906965285 creator A5061151351 @default.
- W2906965285 date "2019-01-04" @default.
- W2906965285 modified "2023-10-18" @default.
- W2906965285 title "It takes a team: a gain-of-function story of p53-R249S" @default.
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