Sharma K, Wang R X, Zhang L Y, Yin D L, Luo X Y, Solomon J C, Jiang R F, Markos K, Davidson W, Scott D W, Shi Y F
Department of Immunology, Holland Laboratory, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855, USA.
Pharmacol Ther. 2000 Dec;88(3):333-47. doi: 10.1016/s0163-7258(00)00096-6.
Apoptotic cell death mediated by the members of the tumor necrosis factor receptor family is an essential process involved in the regulation of cellular homeostasis during development, differentiation, and pathophysiological conditions. Among the cell death receptors comprising the tumor necrosis factor receptor superfamily, CD95/APO-1 (Fas) is the best characterized. The specific interaction of Fas with its cognate ligand, Fas ligand (FasL), elicits the activation of a death-inducing caspase (cysteine aspartic acid proteases) cascade, occurring in a transcription-independent manner. Caspase activation executes the apoptosis process by cleaving various intracellular substrates, leading to genomic DNA fragmentation, cell membrane blebbing, and the exposure of phagocytosis signaling molecules on the cell surface. Recent studies have shown that the Fas/FasL pathway plays an important role in regulating the life and death of the immune system through activation-induced cell death. In addition, these molecules have been implicated in aging, human immunodeficiency virus infection, drug abuse, stress, and cancer development. In this review, we will focus on the mechanisms that regulate Fas and FasL expression, and how their deregulation leads to diseases.
由肿瘤坏死因子受体家族成员介导的凋亡性细胞死亡是一个重要过程，参与发育、分化及病理生理状态下细胞稳态的调节。在构成肿瘤坏死因子受体超家族的细胞死亡受体中，CD95/APO-1（Fas）是研究最为深入的。Fas与其同源配体Fas配体（FasL）的特异性相互作用引发死亡诱导半胱天冬酶（半胱氨酸天冬氨酸蛋白酶）级联反应的激活，该反应以不依赖转录的方式发生。半胱天冬酶激活通过切割各种细胞内底物来执行凋亡过程，导致基因组DNA片段化、细胞膜起泡，并使吞噬作用信号分子暴露于细胞表面。最近的研究表明，Fas/FasL途径通过激活诱导的细胞死亡在调节免疫系统的生死过程中发挥重要作用。此外，这些分子还与衰老、人类免疫缺陷病毒感染、药物滥用、应激和癌症发展有关。在本综述中，我们将重点关注调节Fas和FasL表达的机制，以及它们的失调如何导致疾病。
