Molecular cloning of a Src protease

Src 蛋白酶的分子克隆

• 批准号: 13670516
• 负责人: ITO Nobuyuki
• 金额: $ 2.56万
• 依托单位: Fukui medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670516/
• 关键词: TGF-β; hepatocellular carcinoma; Src; protease; ubiquitination; uniquitination; TGF-P

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.

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。

项目成果

Ito N., Kawata S.: "plasma transforming growth factor-β1 : a useful marker for hepatic fibrosis in Chronic hepatitis C"Trends in Gastroenterdogy and hepatology. 364-366 (2001)

Ito N.，Kawata S.：“血浆转化生长因子-β1：慢性丙型肝炎肝纤维化的有用标记”胃肠病学和肝病学趋势 364-366 (2001)。

Sakuda S, Tamura S, Yamada A, Miyagawa J, Yamamoto K, Kiso S, Ito N, Higashiyama S, Taniguchi N, Kawata S., Matsuzawa Y: "NF-kB activation in non-parenchymal liver cells after partial hepatectomy in rats : possible involvement in expression of heperin-bin

Sakuda S、Tamura S、Yamada A、Miyakawa J、Yamamoto K、Kiso S、Ito N、Higashiyama S、Taniguchi N、Kawata S.、Matsuzawa Y：“大鼠部分肝切除术后非实质肝细胞中的 NF-kB 激活

Ito N., Kawata S.: "Plasma transforming growth factor β1 : a useful marker for hepatic fibrosis in chronic hepatitis C"Trends in Gastroenterology and Hepatology. 364-366 (2001)

Ito N.，Kawata S.：“血浆转化生长因子 β1：慢性丙型肝炎肝纤维化的有用标志物”胃肠病学和肝病学趋势 364-366 (2001)。

Saeki A., Ito N., et al.: "Frequent impairment of the spindle assembly checkpoint in hepatocellular carcinoma"Cancer. 94(7). 2047-2054 (2002)

Saeki A.、Ito N. 等人：“肝细胞癌中纺锤体装配检查点的频繁损伤”癌症。

Sakuda S, Ito N, et al.: "Activation of signal transducer and activator transcription 3 and expression of suppressor of cytokine signal 1 during liver regeneration in rats"J. Hepatol. 36(3). 378-384 (2002)

Sakuda S, Ito N, et al.：“大鼠肝再生过程中信号转导子和激活子转录 3 的激活以及细胞因子信号 1 抑制子的表达”J.