The Joint Center for Infection and Immunity between Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou, 510623, China.
Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
Acta Biochim Biophys Sin (Shanghai). 2020 May 26;52(5):467-474. doi: 10.1093/abbs/gmaa016.
Gasdermins (GSDMs) belong to a protein superfamily that is found only in vertebrates and consists of GSDMA, GSDMB, GSDMC, GSDMD, DFNA5 (a.k.a. GSDME) and DFNB59 (a.k.a. Pejvakin (PJVK)) in humans. Except for DFNB59, all members of the GSDM superfamily contain a conserved two-domain structure (N-terminal and C-terminal domains) and share an autoinhibitory mechanism. When the N-terminal domain of these GSDMs is released, it possesses pore-forming activity that causes inflammatory death associated with the loss of cell membrane integrity and release of inflammatory mediators. It has also been found that spontaneous mutations occurring in the genes of GSDMs have been associated with the development of certain autoimmune disorders, as well as cancers. Here, we review the current knowledge of the expression profile and regulation of GSDMs and the important roles of this protein family in inflammatory cell death, tumorigenesis and other related diseases.
Gasdermins (GSDMs) 属于一个仅在脊椎动物中发现的蛋白质超家族，由 GSDMA、GSDMB、GSDMC、GSDMD、DFNA5（又名 GSDME）和 DFNB59（又名 Pejvakin (PJVK)) 组成。除了 DFNB59 之外，GSDM 超家族的所有成员都包含一个保守的双结构域结构（N 端和 C 端结构域），并具有自动抑制机制。当这些 GSDM 的 N 端结构域被释放时，它具有形成孔的活性，导致与细胞膜完整性丧失和炎症介质释放相关的炎症性死亡。还发现，GSDM 基因中发生的自发突变与某些自身免疫性疾病以及癌症的发展有关。在这里，我们综述了 GSDMs 的表达谱和调控以及该蛋白家族在炎症性细胞死亡、肿瘤发生和其他相关疾病中的重要作用的最新知识。
