PAK5-SIRT5-GLUL复合物内翻译后修饰相互调节在乳腺癌谷氨酰胺代谢中的作用及机制

PAK5过表达与乳腺癌进程相关，谷氨酰胺代谢重编程在乳腺癌进程中具有重要意义，但PAK5过表达在乳腺癌谷氨酰胺代谢重编程中的作用及机制尚不清楚。本项目前期工作筛选出PAK5新的互作蛋白SIRT5。已初步证实二者在线粒体中直接相互作用，且PAK5与SIRT5通过翻译后修饰互相增加蛋白质稳定性。重要的是，PAK5与SIRT5同时作用于谷氨酰胺合酶GLUL，且临床数据分析表明PAK5与SIRT5及GLUL表达具有相关性。本课题旨在进一步阐明 PAK5-SIRT5-GLUL复合物蛋白质间的翻译后修饰相互调节机制；明确PAK5-SIRT5-GLUL复合物调节谷氨酰胺代谢的具体机制，证实PAK5-SIRT5-GLUL复合物与临床乳腺癌分子分型及病人预后的相关性。通过上述研究，我们将明确PAK5-SIRT5-GLUL复合物在乳腺癌谷氨酰胺代谢中的作用及机制，为临床乳腺癌的诊断及治疗提供重要理论依据。

PAK5 overexpression is associated with breast cancer progression. Glutamine metabolic reprogramming is of great significance in breast cancer progression, but the role and mechanism of PAK5 overexpression in breast cancer glutamine metabolic reprogramming is still unclear. The preliminary work of this project screened out the PAK5 new binding protein SIRT5. It has been preliminarily confirmed that the two interact directly in mitochondria, and PAK5 and SIRT5 increase mutual protein stability through post-translational modification. It is important that PAK5 and SIRT5 act on glutamine synthase GLUL at the same time, and clinical data analysis shows that PAK5 is correlated with SIRT5 and GLUL expression. This project aims to further clarify the mutual regulation mechanism of the post-translational modification of PAK5-SIRT5-GLUL complex proteins; to clarify the specific mechanism of PAK5-SIRT5-GLUL complex regulating glutamine metabolism, and to confirm the correlation between PAK5-SIRT5-GLUL complex and clinical breast cancer molecular typing, patient survival and prognosis. Through the above research, we will clarify the role and mechanism of PAK5-SIRT5-GLUL complex in breast cancer glutamine metabolism, and provide an important theoretical basis for clinical breast cancer diagnosis and treatment.