title: The GAS41-PP2Cbeta complex dephosphorylates p53 at serine 366 and regulates its stability.
abstract: 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.affiliation: Institute of Molecular Biosciences, Massey University, Palmerston North 4442, New Zealand. J.Park@massey.ac.nz
authors.forename: Jeong Hyeon
authors.initials: JH
authors.lastname: Park
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Smith
authors.forename: Sheau-Yann
authors.initials: SY
authors.lastname: Shieh
authors.forename: Robert G
authors.initials: RG
authors.lastname: Roeder
mesh_terms: D002460:Cell Line; D005910:Glioma / Q000235:genetics / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D000071636:Protein Phosphatase 2C; D055550:Protein Stability; D012694:Serine / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects; D015854:Up-Regulation / Q000235:genetics / Q000528:radiation effects
chemical_list: D046912:Multiprotein Complexes; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C109446:YEATS4 protein, human; D012694:Serine; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C