头帕肿瘤综合征蛋白与肿瘤坏死因子受体介导的坏死样凋亡

CYLD and tumor necrosis factor receptor-mediated necroptosis

头帕肿瘤综合征蛋白(cylindromatosis,CYLD)是一种去泛素化酶,其C-末端USP结构域具有催化功能,可移除受体相互作用蛋白激酶1(receptor interacting protein kinase 1,RIPK1)的K63连接泛素链,调节RIPK1的泛素化水平,从而参与调节肿瘤坏死因子受体1(tumor necrosis factor receptor 1,TNFR1)介导的RIPK依赖的细胞坏死样凋亡等病理生理过程。阐明C YLD对RIPK1去泛素化调节的详细机制,寻找针对CYLD的特异性抑制剂,可为与坏死样凋亡相关的损伤与疾病提供治疗的新策略。

Cylindromatosis（CYLD） is a deubiquitinase, which regulates the level of ubiquitination for receptor interacting protein kinase 1（RIPK1） by removing lysine 63-linked polyubiquitin chains. CYLD involves in the regulation of RIPK-dependent and tumor necrosis factor receptor 1（TNFR1）-mediated cell necroptosis and other physiological and pathological processes. Clarification of the detailed mechanism of CYLD on RIPK1 and identification of specific inhibitor of this process will provide a new strategy for the treatment of the diseases associated with necroptosis.