PP2A interaction with Rb2/p130 mediates translocation of Rb2/p130 into the nucleus in all-Trans retinoic acid-treated ovarian carcinoma cells

Authors

  • Enkhtsetseg Purev,

    1. Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania
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  • Dianne R. Soprano,

    1. Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania
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  • Kenneth J. Soprano

    Corresponding author
    1. Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania
    • Department of Microbiology and Immunology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140.
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Abstract

One of the mechanisms by which all-trans retinoic acid (ATRA) has been shown to suppress the growth of CAOV3 ovarian carcinoma cells involves an increase in the accumulation of Rb2/p130 protein, a member of the retinoblastoma family of tumor suppressors. This increase in accumulation of RB2/p130 by ATRA results from increased stability of Rb2/p130 protein as a result of an increase in dephosphorylation of the protein by the serine/threonine phosphatase PP2A. We show that upon ATRA treatment, PP2A interacts with the Rb2/p130 C-terminus and specifically dephosphorylates two residues (S1080 and T1097) adjacent to NLS1 and NLS2 of Rb2/p130. Moreover, co-immunoprecipitation studies reveal that Rb2/p130 can form a complex with the nuclear transport proteins, importin α and importin β, binding to the same dephosphorylated NLS1 and NLS2 sites. Finally, mutation of S1080 and T1097 results in retension of Rb2/p130 in the cytoplasm. Our studies suggest that one mechanism by which ATRA treatment of CAOV3 cells induces G0/G1 arrest involves the recruitment of PP2A to the C-terminus of Rb2/p130, resulting in the dephosphorylation of the S1080 and T1097 adjacent to the NLS and the subsequent interaction of Rb2/p130 with importins leading to transport of the Rb2/p130 to the nucleus where it inhibits cell-cycle progression. J. Cell. Physiol. 226: 1027–1034, 2011. © 2010 Wiley-Liss, Inc.

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