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- W2116787167 abstract "The RAS–ERK pathway is known to play a pivotal role in differentiation, proliferation and tumour progression. Here, we show that Erk downregulates Forkhead box O 3a (FOXO3a) by directly interacting with and phosphorylating FOXO3a at Ser 294, Ser 344 and Ser 425, which consequently promotes cell proliferation and tumorigenesis. The ERK-phosphorylated FOXO3a degrades via an MDM2-mediated ubiquitin-proteasome pathway. However, the non-phosphorylated FOXO3a mutant is resistant to the interaction and degradation by murine double minute 2 (MDM2), thereby resulting in a strong inhibition of cell proliferation and tumorigenicity. Taken together, our study elucidates a novel pathway in cell growth and tumorigenesis through negative regulation of FOXO3a by RAS–ERK and MDM2." @default.
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- W2116787167 date "2008-01-20" @default.
- W2116787167 modified "2023-10-17" @default.
- W2116787167 title "ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation" @default.
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- W2116787167 doi "https://doi.org/10.1038/ncb1676" @default.
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