PDF(Pubmed)
Abstract：
CYLD lysine 63 deubiquitinase (CYLD) is a ubiquitin hydrolase with important roles in immunity and cancer. Complete CYLD ablation, truncation and expression of alternate isoforms, including short CYLD, drive distinct phenotypes and offer insights into CYLD function in inflammation, cell death, cell cycle progression and cell transformation. Research in diverse model systems has shown that these are mediated via CYLD regulation of cellular pathways including the NF-κB, Wnt and TGF-β pathways. Recent biochemical advances and models have offered new insights into the regulation and function of CYLD. In addition, recent discoveries of gain-of-function germline pathogenic CYLD variants in patients with a neurodegenerative phenotype contrast with the more widely known loss-of-function mutations seen in patients with CYLD cutaneous syndrome and with sporadic cancers. Here, we provide a current review of mechanistic insights into CYLD function gained from CYLD animal models, as well as an update on the role of CYLD in human disease.
摘要：
CYLD赖氨酸63去泛素酶（CYLD）是一种泛素水解酶，在免疫和癌症中具有重要作用。完全CYLD消融,替代同工型的截短和表达，包括短周期，驱动不同的表型，并提供对炎症中CYLD功能的见解，细胞死亡,细胞周期进程和细胞转化。在不同模型系统中的研究表明，这些是通过CYLD调节细胞通路，包括NF-κB，Wnt和TGF-β途径。最近的生化进展和模型为CYLD的调节和功能提供了新的见解。此外,最近发现神经退行性表型患者的生殖系致病性CYLD变异与CYLD皮肤综合征和散发性癌症患者中更广为人知的功能丧失突变形成对比。这里,我们提供了从CYLD动物模型获得的CYLD功能的机理见解的最新综述，以及CYLD在人类疾病中的作用的更新。
