Molecular cloning of a Src protease

我们已经表明，对TGF-β的反应性的丧失有助于肝细胞癌中的自主细胞增殖。我们还发现，在TGF-β抑制增殖的细胞中，TGF-β降低Src蛋白。这些结果表明，TGF-β诱导的某些蛋白酶可能调节细胞内Src的含量。本项目旨在寻找并克隆该蛋白酶。然而，我们在该蛋白酶的测定系统的可靠性方面存在问题，现在我们正在努力建立该系统。另一方面，我们发现TGF-β诱导的Src降解似乎在很大程度上依赖于TGF-β增加的Src泛素化。我们正在研究TGF-β诱导肝癌细胞Src泛素化的机制。

We have shown that loss of responsiveness against TGF-β contributes to the autonomous cell proliferation in hepatocellular carcinoma. We have also shown that Src protein was decreased by TGF-β in the cells whose proliferation was inhibited by TGF-β. These results indicate that some protease which is induced by TGF-β may regulate intracellular amounts of Src. This project aimed to find out to clone the protease. However, we have problems concerning with the reliability of the assay system for this protease and now we are fighting to establish the system. On the other hand, we found that the TGF-β-induced Src degradation seems to largely depend on increased Src ubiquitination by TGF-β. We are investigating the mechanisms of TGF-β-induced Src ubiquitination in hepatoma cells.