ZDHHC4介导的GSK3β棕榈酰化修饰调控胶质瘤发生发展的作用机制

棕榈酰基化修饰是一种由棕榈酰基转移酶介导的蛋白质翻译修饰方式，异常修饰导致的蛋白质功能变化与肿瘤等疾病密切相关，但在胶质瘤发生发展中的作用仍不清楚。我们前期研究发现，在胶质瘤组织中的棕榈酰转移酶ZDHHC4高丰度的表达，且发现GSK3β是一个特异性的修饰底物，ZDHHC4通过影响GSK3β活性调节胶质瘤细胞的增殖与肿瘤细胞干性等恶性表型，但涉及的相互作用网络、信号转导途径不甚明了。本项目拟采用分子生物学、细胞生物学、化学生物学及实验动物学等手段，进一步揭示ZDHHC4表达与胶质瘤发生发展的关联性，阐明ZDHHC4介导的蛋白翻译后修饰在胶质瘤恶性发生发展中作用网络、信号传导途径等作用机制，探索其功能异常引起的病理机制，为相关疾病临床治疗与研究提供理论基础。

Palmitoylation is a protein post-translational modification mediated by palmitoyltransferase (PATs). The protein functional dynamics caused by abnormal expression and post-modification are closely related to diseases such as tumors, but the mechanism in the development of glioma is still unclear. Our previous study found that the highly expression of ZDHHC4, one of palmitoyltransferase, in glioma. And GSK3β is a specific substrate of ZDHHC4, the proliferation and cancer cell stemness of glioma cells were affected through ZDHHC4/GSK3β signaling. However, the interaction networks and signal transduction pathways involved in the tumorigenesis of glioma are not clear. In this project, we try to use multiple technologies including molecular biology, cell biology, chemical biology and experimental zoology, to further reveal the relationship between ZDHHC4 expression and the development of glioma, to elucidate the networks and signaling pathways by the ZDHHC4-mediated palmitoylation of GSK3β in the development of glioma, and to explore the pathological mechanisms caused by its abnormal function, so as to provide a theoretical basis for the clinical treatment and research.