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Pubmed ID :21317290
Publication Date : //

The GAS41-PP2Cbeta complex dephosphorylates p53 at serine 366 and regulates its stability.


The p53 tumor suppressor is principally regulated by post-translational modifications and proteasome-dependent degradation. Various kinases have been shown to phosphorylate p53, but little is known about the counteracting phosphatases. We demonstrate here that the newly identified complex GAS41-PP2Cβ, and not PP2Cβ alone, is specifically required for dephosphorylation of serine 366 on p53. Ectopic expression of GAS41 and PP2Cβ reduces UV radiation-induced p53 up-regulation, thereby increasing the cell survival upon genotoxic DNA damage. To our knowledge, the GAS41-PP2Cβ complex is the first example in which substrate specificity of a PP2C family member is controlled by an associated regulatory subunit. Because GAS41 is frequently amplified in human gliomas, our finding illustrates a novel oncogenic mechanism of GAS41 by p53 dephosphorylation.

Authors : Park Jeong Hyeon , Smith Rebecca J , Shieh Sheau-Yann , Roeder Robert G ,

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