The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit.

Durfee, Tim; Becherer, Kathleen; Chen, Phang-Lang; Yeh, Shiou Hwei; Yang, Yanzhu; Kilburn, April E.; Lee, Wen‐Hwa; Elledge, Stephen J.

doi:10.1101/gad.7.4.555

Cited by 1,442 publications

(1,315 citation statements)

References 80 publications

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“…Downstream targets of p53 at the G 2 control are not known so far. On the other hand, the observations that pRB interacts with several proteins potentially involved in mitosis Zhu et al, 1995;Thomas et al, 1996) as well as the fact that pRB exhibits M phase-speci®c binding to a protein phosphatase type 1 which may be related to cell cycle-speci®c changes of the phosphorylation status of pRB (Durfee et al, 1993) is of particular interest. It is possible that PyLT interferes with such functions of pRB resulting in failures during mitosis.…”

Section: Mrc5mentioning

confidence: 99%

Polyomavirus large T antigen-dependent DNA amplification

et al. 1997

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DNA ampli®cation is a readily measurable indicator for genome destabilization. Contrary to normal senescing cells, those of most immortal or transformed cell lines are karyotypically unstable and permissive for ampli®ca-tion. Permissivity for ampli®cation can be generated by gene products of several DNA tumor viruses whereby their interaction with the tumorsuppressor protein p53 is important. p53 is the major protein involved in check point control of DNA damage. Polyomavirus large T antigen is also involved in immortalization and transformation of cells but it does not interact with p53. We, therefore, examined whether this protein could still make the non-permissive cell line REF52 permissive for gene ampli®cation. To this end REF52 cell lines were constructed which conditionally expressed the wild type polyomavirus large T antigen or a mutant form unable to bind the retinoblastoma protein. Using the inhibitor of de novo pyrimidine biosynthesis, phosphonoacetyl-L-aspartate (PALA), as selective agent we found that PALA resistant cells arise with a frequency of about 5610 75 and that the interaction of polyomavirus large T protein with the retinoblastoma protein or another related pocket protein is important for this to occur. PALA resistant cells have an increased number of chromosomes and dicentric chromosomes which are considered as starting point for DNA structures characteristic for ampli®ed DNA. Such structures were indeed found with the help of uorescence in situ hybridization. PALA resistant cells appear normal with respect to p53. Our data indicate that PALA induces a G 1 block which can be partially overcome by polyomavirus large T protein by its interaction with E2F-pocket protein complexes providing further evidence that these complexes are downstream targets of p53.

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Section: Mrc5mentioning

confidence: 99%

Polyomavirus large T antigen-dependent DNA amplification

et al. 1997

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“…The retinoblastoma protein has been shown to interact directly with the protein phosphatase 1 (PP1) catalytic subunit during the M phase of the cell cycle, when pRb is known to be dephosphorylated (Durfee et al, 1993;. Moreover, a high molecular weight form of PP1 found in mitotic cell extracts was shown to be able to dephosphorylate pRb in vitro .…”

Section: Introductionmentioning

confidence: 99%

Functional interaction between a novel protein phosphatase 2A regulatory subunit, PR59, and the retinoblastoma-related p107 protein

1999

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The proteins of the retinoblastoma family are potent inhibitors of cell cycle progression. It is well documented that their growth-inhibitory activity can be abolished by phosphorylation on serine and threonine residues by cyclin dependent kinases. In contrast, very little is known about the dephosphorylation of retinoblastoma-family proteins. We report here the isolation, by virtue of its ability to associate with p107, of a novel Protein Phosphatase 2A (PP2A) regulatory subunit, named PR59. PR59 shares sequence homology with a known regulatory subunit of PP2A, PR72, but di ers from PR72 in its expression pattern and its functional properties. We show that PR59 co-immunoprecipitates with the PP2A catalytic subunit, indicating that PR59 is a genuine component of PP2A holo-enzymes. In vivo, PR59 associates speci®cally with p107, but not with pRb. Elevated expression of PR59 results in dephosphorylation of p107, but not of pRb, and inhibits cell proliferation by causing cells to accumulate in G1. These data support a model in which the distinct PP2A regulatory subunits act to target the PP2A catalytic subunit to speci®c substrates and suggest a role for PP2A in regulation of p107.

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“…We chose to use Ski sequence derived from v-Ski as bait since all identi®ed biological activity is shared between c-Ski and the smaller v-Ski (Colmenares et al, 1991a;Sutrave et al, 1990a). V-Ski sequence was cloned into the two-hybrid GAL4 DNA binding vector pGBT9 and the resultant plasmid was used to screen a previously constructed two-hybrid library made from cDNA of EBV transformed human lymphoid cells (Durfee et al, 1993).…”

Section: Identi®cation Of a Ski Binding Partnermentioning

confidence: 99%

“…The yeast two-hybrid system was used to screen a lymphoid cell library as described (Bartel et al, 1993;Durfee et al, 1993). The pGTB9/v-Ski plasmid was used as bait and co-transformed with the cDNA library into yeast strain Y153 (Durfee et al, 1993) using a lithium acetate protocol (Schiestel and Gietz, 1989).…”

Section: Yeast Two-hybrid Screenmentioning

confidence: 99%

“…The pGTB9/v-Ski plasmid was used as bait and co-transformed with the cDNA library into yeast strain Y153 (Durfee et al, 1993) using a lithium acetate protocol (Schiestel and Gietz, 1989). Approximately 2610 6 transformants were plated onto synthetic complete (SC) media lacking tryptophan, leucine, and histidine, but including 25 mM 3-amino-triazole (Sigma).…”

Section: Yeast Two-hybrid Screenmentioning

confidence: 99%

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