Disruption of the interaction between retinoblastoma protein and 70 kD heat shock protein leads to growth acceleration of tumor cells

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Retinoblastoma protein (pRb) is a phosphoprotein regulating cell growth. During G1 phase in the cell cycle, pRb is dephosphorylated and inhibits the progression to S phase. Previously we demonstrated that 70 kDa heat shock protein (HSP70) was associated with dephosphorylated pRb in vivo and in vitro, and mapped the HSP70 binding region of pRb. In this report we analyzed the consequences of disruption of the HSP70-pRb interaction in cells. Recombinant fusion proteins containing the 11 amino acid HIV TAT transduction domain and HSP70 binding domain (residues 301-372, RbHBD) or N-terminal non-binding region of pRb (RbNTR) were produced. The TAT fusion proteins were introduced into cells by addition into culture medium. TAT-RbHBD protein, but not TAT-RbNTR protein, was capable of binding to HSP 70 in the cells. Transduction of TAT-RbHBD protein inhibited the association of HSP70 to pRb in cells; however, TAT-RbNTR fusion protein failed to do so. Strikingly, transduction of TAT-RbHBD fusion protein promoted proliferation of HOS cells, Jurkat cells and U-937 cells expressing functional pRb, but not of SAOS cells lacking pRb. In addition, HOS cells treated with heat shock became more resistant to the effect of TAT-RbHBD protein. These data indicate that disruption of the HSP70-pRb interaction leads to growth acceleration of cells. Our study revealed an important in vivo role of HSP700-pRb interaction in cell cycle control.

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  • Tumor Research

    Tumor Research 41 43-57, 2006

    Sapporo Medical University

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