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

Oncogene volume 18, pages 515–524 (1999)Cite this article

Abstract

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 differs 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 specifically 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 specific substrates and suggest a role for PP2A in regulation of p107.

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Acknowledgements

We thank Helen Brantjes for assistance, Natasja Andjelkovic and Dr Brian Hemmings for the kind gift of various plasmids and advice, Dr Ron Kerkhoven for providing RNA, Tony van Hamersfeld for assistance in generating PR59 antiserum and Daniel Peeper for critical reading of this manuscript. This work was supported by a grant from the Netherlands Organization for Scientific Research (NWO). The nucleotide sequence reported in this paper has been submitted to the Genbank database, and has been assigned accession number AF050165.

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  1. Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, 121 Plesmanlaan, CX Amsterdam, 1066, The Netherlands

    P Mathijs Voorhoeve, E Marielle Hijmans & René Bernards

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Voorhoeve, P., Hijmans, E. & Bernards, R. Functional interaction between a novel protein phosphatase 2A regulatory subunit, PR59, and the retinoblastoma-related p107 protein. Oncogene 18, 515–524 (1999). https://doi.org/10.1038/sj.onc.1202316

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