Nihei T, Takahashi S, Sagae S, Sato N, Kikuchi K
Department of Pathology, Sapporo Medical College, Japan.
Cancer Res. 1993 Apr 1;53(7):1702-5.
Both the tumor suppressor gene products, the retinoblastoma sensitivity gene product pRb110 and p53, are found in oligomer complexes with the oncogene products of the DNA tumor viruses. It has been demonstrated that p53 binds to the M(r) 70,000 heat shock protein family. However, the protein association of pRb110 with the M(r) 70,000 heat shock protein family is not yet known. We analyzed the immunoprecipitates made with TYK-nu human ovarial carcinoma cell lysate and anti-pRb110 or anti-heat shock protein monoclonal antibodies. In this paper, we demonstrate that pRb110 is associated with the M(r) 73,000 heat shock cognate protein, but not with the M(r) 72,000 heat shock protein. This selective protein association was also detected in HeLa cervical carcinoma cells. Furthermore, the protein complexes of the M(r) 73,000 heat shock cognate protein and pRb110 were dissociated with the presence of ATP, but not with ADP and the nonhydrolyzable ATP analogue, ATP gamma S. This indicates that the dissociation is dependent on the ATP hydrolysis. These data may suggest an as yet undefined important role of M(r) 73,000 heat shock cognate protein in the cell growth control in collaboration with pRb110.
肿瘤抑制基因产物视网膜母细胞瘤敏感基因产物pRb110和p53,都存在于与DNA肿瘤病毒癌基因产物形成的寡聚体复合物中。已经证明p53与分子量为70,000的热休克蛋白家族结合。然而,pRb110与分子量为70,000的热休克蛋白家族的蛋白质关联尚不清楚。我们分析了用TYK-nu人卵巢癌细胞裂解物与抗pRb110或抗热休克蛋白单克隆抗体制备的免疫沉淀物。在本文中,我们证明pRb110与分子量为73,000的热休克同源蛋白相关,但与分子量为72,000的热休克蛋白无关。在人宫颈癌HeLa细胞中也检测到了这种选择性的蛋白质关联。此外,分子量为73,000的热休克同源蛋白和pRb110的蛋白质复合物在有ATP存在时解离,但在有ADP和不可水解的ATP类似物ATPγS存在时不解离。这表明这种解离依赖于ATP水解。这些数据可能提示分子量为73,000的热休克同源蛋白在与pRb110协同控制细胞生长中具有尚未明确的重要作用。