Inactivation of pRB-related proteins p130 and p107 mediated by the J domain of simian virus 40 large T antigen.
作者： J A DeCaprio , H Stubdal , J Zalvide , K S Campbell , C Schweitzer
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摘要: Inactivation of the retinoblastoma tumor suppressor protein (pRB) contributes to tumorigenesis in a wide variety cancers. In contrast, role two pRB-related proteins, p130 and p107, oncogenic transformation is unclear. The LXCXE domain simian virus 40 large T antigen (TAg) specifically binds pRB, p130. We have previously shown that N terminus TAg cooperate alter phosphorylation state p107. Here, we demonstrate promotes degradation required for this activity. has homology J DnaJ family molecular chaperone proteins. Mutants with mutations J-domain region are defective altering p107 degradation. A heterologous from human can functionally substitute effect on stability. further confers growth advantage wild-type mouse embryo fibroblasts (MEFs) but dispensable case MEFs lacking both This indicates overlapping growth-suppressing activities whose inactivation mediated by TAg.
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