HAX-1调控非受体酪氨酸激酶c-Abl活性与降解的分子机制

项目名称： HAX-1调控非受体酪氨酸激酶c-Abl活性与降解的分子机制

项目编号： No.31270798

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 曹诚

作者单位： 中国人民解放军军事医学科学院

项目金额： 80万元

中文摘要： 非受体酪氨酸激酶c-Abl参与哺乳动物细胞内氧化应激过程调控。 反应氧（ROS) 激活胞浆中的c-Abl，调节过氧化氢酶及谷胱甘肽过氧化物酶降解细胞中H2O2，从而调节细胞对氧化损伤的抵抗力。但是c-Abl被氧化应激激活的机制任不完全清楚。前期研究结果表明，细胞内ROS可以显著促进抗凋亡蛋白HAX-1与非受体酪氨酸激酶c-Abl直接相互作用，从而激活c-Abl，导致与c-Abl活性相关关键位点酪氨酸自磷酸化，同时调控c-Abl通过泛素－蛋白酶体降解。这些初步结果提示，HAX-1是参与氧化应激条件下激活c-Abl的重要分子，激活c-Abl促进细胞内ROS清除可能是HAX-1发挥抗凋亡作用的重要分子机制。该研究为解释HAX-1的抗凋亡机制、对于深入认识c-Abl非受体酪氨酸激酶的活性调节及其氧化应激下生物学功能的调控机制提供新的重要理论依据。

中文关键词： HAX-1；c-Abl；泛素化；抗凋亡；

英文摘要： Non-receptor tyrosine kinase c-Abl was involved in oxidative stress. It was activated by reactive oxigenspecies,and regulates the removal of H2O2 by activating catalase and gluthathione peroxidase 1.The mechanism by which c-Abl was activated by ROS kept largly unknown. Our previous work demonstrated that c-Abl interacted with the anti-apoptotic protein HAX-1, and the interaction was significantly potentiated by cellular ROS. c-Abl was activated by HAX-1, and then subjected to ubiquitin-proteasomaldegradation. These results suggested that HAX-1 plays important role in the activation of c-Abl by oxidative stress, and c-Abl regulated removal of cellular ROS may responsible for the anti-apoptotic effect of HAX-1. The further research by the project may provide insight understanding of the mechanism how c-Abl was regulated as well as the anti-apoptotic mechanism of HAX-1.

英文关键词： HAX-1；c-Abl；ubiquitination；anti-apoptosis；