title: PP2A: more than a reset switch to activate pRB proteins during the cell cycle and in response to signaling cues.
abstract: In their active hypophosphorylated state, members of the retinoblastoma family of pocket proteins negatively regulate cell cycle progression at least in part by repressing expression of E2F-dependent genes. Mitogen-dependent activation of G1 and G1/S Cyclin Dependent Kinases (CDKs) results in coordinated hyperphosphorylation and inactivation of these proteins, which no longer bind and repress E2Fs. S and G2/M CDKs maintain pocket protein hyperphosphorylated through the end of mitosis. The inactivating action of inducible CDKs is opposed by the Ser/Thr protein phosphatases PP2A and PP1. Various trimeric PP2A holoenzymes have been implicated in dephosphorylation of pocket proteins in response to specific cellular signals and stresses or as part of an equilibrium with CDKs throughout the cell cycle. PP1 has specifically been implicated in dephosphorylation of pRB in late mitosis and early G1. This review is particularly focused on the emerging role of PP2A as a major hub for integration of growth suppressor signals that require rapid inactivation of pocket proteins. Of note, activation of particular PP2A holoenzymes triggers differential activation of pocket proteins in the presence of active CDKs.
authors.affiliation: a Fels Institute for Cancer Research and Molecular Biology and Department of Biochemistry; Temple University School of Medicine ; Philadelphia , PA USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Kurimchak
authors.forename: Xavier
authors.initials: X
authors.lastname: Graña
mesh_terms: D000818:Animals; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D050684:E2F Transcription Factors / Q000378:metabolism; D007399:Interphase; D018384:Oxidative Stress; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000737:chemistry / Q000378:metabolism*; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D050684:E2F Transcription Factors; D021122:Protein Subunits; D016160:Retinoblastoma Protein; D018844:Cyclin-Dependent Kinases; D054648:Protein Phosphatase 2
keywords: B55α; B55δ; E2F; PP2A; PPP2R2A PP1; PR70; cell cycle; chondrocyte; p107; p130; pRB; retinoblastoma