title: B55alpha PP2A holoenzymes modulate the phosphorylation status of the retinoblastoma-related protein p107 and its activation.
abstract: Pocket proteins negatively regulate transcription of E2F-dependent genes and progression through the G(0)/G(1) transition and the cell cycle restriction point in G(1). Pocket protein repressor activities are inactivated via phosphorylation at multiple Pro-directed Ser/Thr sites by the coordinated action of G(1) and G(1)/S cyclin-dependent kinases. These phosphorylations are reversed by the action of two families of Ser/Thr phosphatases: PP1, which has been implicated in abrupt dephosphorylation of retinoblastoma protein (pRB) in mitosis, and PP2A, which plays a role in an equilibrium that counteracts cyclin-dependent kinase (CDK) action throughout the cell cycle. However, the identity of the trimeric PP2A holoenzyme(s) functioning in this process is unknown. Here we report the identification of a PP2A trimeric holoenzyme containing B55α, which plays a major role in restricting the phosphorylation state of p107 and inducing its activation in human cells. Our data also suggest targeted selectivity in the interaction of pocket proteins with distinct PP2A holoenzymes, which is likely necessary for simultaneous pocket protein activation.
authors.affiliation: Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Girish
authors.initials: G
authors.lastname: Jayadeva
authors.forename: Alison
authors.initials: A
authors.lastname: Kurimchak
authors.forename: Judit
authors.initials: J
authors.lastname: Garriga
authors.forename: Elena
authors.initials: E
authors.lastname: Sotillo
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Davis
authors.forename: Dale S
authors.initials: DS
authors.lastname: Haines
authors.forename: Marc
authors.initials: M
authors.lastname: Mumby
authors.forename: Xavier
authors.initials: X
authors.lastname: Graña
mesh_terms: D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism; D020035:Holoenzymes / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation / Q000502:physiology; D055503:Protein Multimerization / Q000502:physiology*; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D050720:Retinoblastoma-Like Protein p107 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D050684:E2F Transcription Factors; D020035:Holoenzymes; C493844:RBL1 protein, human; D050720:Retinoblastoma-Like Protein p107; D018844:Cyclin-Dependent Kinases; C517189:PPP2CA protein, human; D054648:Protein Phosphatase 2