AKT的激活是PTEN缺失型胶质母细胞瘤获得高侵袭能力的主要原因之一，阐明PTEN/AKT通路下游的分子机制可为治疗PTEN缺失型胶质母细胞瘤提供了新依据。我们前期发现PTEN缺失介导的AKT激活可抑制ADP核糖基化因子4C（ARL4C）泛素化降解，从而促进肿瘤细胞的侵袭。进一步研究发现泛素连接酶TRIM21能与ARL4C结合，而TRIM21/ARL4C轴参与肿瘤细胞侵袭。同时AKT能够和ARL4C结合，而ARL4C的氨基酸序列存在与P-AKT结合的模体序列。因此我们推测在PTEN缺失型胶质母细胞瘤中，激活的AKT促进了ARL4C磷酸化，进而抑制了TRIM21介导的ARL4C的泛素化降解，获得高侵袭能力。本项目围绕激活的AKT如何抑制ARL4C泛素化降解机制进行探讨，旨在寻找PTEN缺失型胶质母细胞瘤中新的治疗靶点，为蛋白泛素化修饰与肿瘤侵袭提供新理论。

The AKT activation was responsible for high invasiveness in glioblastoma bearing PTEN deficiency, therefore, it provides evidences to elucidate the mechanism the underlying downstream molecular mechanism of PTEN/AKT pathway for treating PTEN deficient glioblastoma. Our former research revealed that the ARL4C ubiquitination might be inhibited by PTEN/AKT signal pathway and that showed that TRIM21, act as E3 ligase, could be combine with ARL4C, Functionally，TRIM21/ARL4C axis was involved in the invasion of tumor cells.Besides, AKT could interact with ARL4C，which shared a partial P-AKT consensus motif. Therefore, we speculate that the activation of AKT interacts and phosphorylates ARL4C, thereby blocking the TRIM21-mediated ubiquitination of ARL4C, which result in high invasion of PTEN-deficient glioblastoma. This project will focus on and investigate the effects and molecular mechanism of AKT activation decreased ARL4C ubiquitination in PTEN-deficient glioblastoma. By this study, we are aimed to seek for a novel target for treatment of PTEN-deficient glioblastoma and to provide theoretics support for ubiqutination and tumor invasion.