Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, Jiangsu, China.
Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, Jiangsu, China.
Biomed Pharmacother. 2022 Sep;153:113467. doi: 10.1016/j.biopha.2022.113467. Epub 2022 Jul 28.
Cells communication in response to extracellular or biophysical stimulus relies on elaborated systems of signal transduction. In the course of most signal pathway, the cascades involve signal protein complexes, which are often assembled by adaptor proteins. Tumor necrosis factor receptor type 1-associated death domain protein (TRADD) is an adaptor molecule involved in various signal pathways and mediating multiple biological activities, including cell survival, cell proliferation, cell differentiation, apoptosis, necroptosis and inflammation. TRADD contains an N terminal tumor necrosis factor receptor-associated factor 2 (TRAF2) binding domain and a C terminal death domain (DD) for interacting with multiple DD-containing proteins. Following activation of specific receptors, such as tumor necrosis factor receptor 1 (TNFR1), death receptor 3 (DR3), tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAILR1, DR4), TRAILR1 (DR5), DR6 and p75 neurotrophin receptor (p75)，TRADD can bind to the receptors, serving as a platform for the recruitment of the downstream molecules for signal propagating and thus mediating various physiological and pathological processes. In this review, we provide a brief overview of the current knowledge on TRADD and discuss the roles of TRADD in infectious and inflammatory diseases, cardiovascular diseases, central nervous system diseases, cancer, endometriosis, hepatocyte proliferation, preterm birth and perinatal development.
细胞对外界或生物物理刺激的通讯依赖于精细的信号转导系统。在大多数信号通路中，级联反应涉及信号蛋白复合物，这些复合物通常由衔接蛋白组装而成。肿瘤坏死因子受体 1 相关死亡结构域蛋白（TRADD）是一种参与多种信号通路的衔接分子，介导多种生物学活性，包括细胞存活、细胞增殖、细胞分化、细胞凋亡、坏死性凋亡和炎症。TRADD 含有一个 N 端肿瘤坏死因子受体相关因子 2（TRAF2）结合域和一个 C 端死亡结构域（DD），用于与多个含有 DD 的蛋白质相互作用。在特定受体（如肿瘤坏死因子受体 1（TNFR1）、死亡受体 3（DR3）、肿瘤坏死因子相关凋亡诱导配体受体 1（TRAILR1、DR4）、TRAILR1（DR5）、DR6 和 p75 神经营养素受体（p75））激活后，TRADD 可以与受体结合，作为募集下游分子进行信号传递的平台，从而介导各种生理和病理过程。在这篇综述中，我们简要概述了 TRADD 的现有知识，并讨论了 TRADD 在感染和炎症性疾病、心血管疾病、中枢神经系统疾病、癌症、子宫内膜异位症、肝细胞增殖、早产和围产期发育中的作用。
