STRIPAK复合物与肿瘤发生

Roles of STRIPAK Complex in Tumorigenesis

STRIPAK是同时包含磷酸酶、激酶及其他辅助支架蛋白在内的超大分子复合物。该复合物在进化上高度保守,调控包括增殖、凋亡、囊泡运输、细胞周期等在内的多种细胞生物学过程,从而在组织器官发育、稳态维持及免疫调节等方面发挥重要功能。近期研究发现,STRIPAK可响应细胞内外信号刺激而组装为包含不同支架蛋白的功能性复合物,其关键组分表达失调或组装紊乱与包括肿瘤在内的多种人类疾病的发生密切相关。该文对近年来针对该复合物的结构、信号网络和生物学功能进行系统综述,以期为该复合物相关的肿瘤基础研究及临床靶向干预提供新的思路和策略。

The STRIPAK(striatin-interacting phosphatase and kinase)is a class of supramolecular complexes conserved in different organisms.Functionally,STRIPAK complexes play essential roles in several biological processes ranging from cell proliferation,apoptosis,vesicle transport to cell cycle regulation.Thus,STRIPAK has been shown to participate in regulating organ development,tissue homeostasis,and immune modulation.Of note,STRIPAK can be assembled into diverse forms and compositions in response to extracellular or intracellular stimuli,dysregulation of which,via either subunit expression or complex formation,is closely related to diverse human diseases including cancer.Here by reviewing the recent advances in understanding the topological structure,signal transduction networks,as well as the physiological and pathological roles of STRIPAK,this paper aims to provide novel insights into understanding of tumorigenesis and targeted strategy for clinical anti-tumor therapy.