網膜芽細胞腫蛋白質における73kDa熱ショック蛋白質会合部位の同定と分子会合の機能的意義の解析

概要

論文の詳細を見る
Retinoblastoma protein (pRb) interacts with transcriptional factors and, particulary, dephosphorylated pRb functions as a negative regulator of cell cycle. We have previously demonstrated that dephosphorylated pRb was associated with 73kDa heat shock cognate protein (HSC73) in certain tumor cell lines. In this experiment, we analyzed the interaction between these two proteins in vitro and determined the HSC73-binding region of pRb by using GST-deletion mutant pRb fusion proteins and synthetic peptides corresponding to the amino acid sequence of pRb. Our data showed that HSC73 interacted directly with a novel region which was located in N-terminal 328-340 amino acid residues outside the pocket region of pRb. Furthermore, we analyzed the function of HSC73 in its interaction with pRb in vitro. The analysis using native polyacrylamide gel electrophoresis indicated that the HSC73 could confer the conformational change on pRb, and might protect the aggregation. Dephosphorylated pRb, but not phosphorylated pRb was degraded by the liver-derived cytosolic extract when the interaction with HSC73 was blocked by the synthetic peptide. These data suggest that HSC73 acts as the molecular chaperone selectively for the dephosphorylated pRb, thereby potentiating the pRb function as the inhibitory regulator of cell cycle and, further, cell proliferation.
札幌医科大学の論文
1997-04-01