Schneider Jessica S, Glickman Michael S
Immunology Program, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, USA; Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Biomedical Sciences, USA.
Biochim Biophys Acta. 2013 Dec;1828(12):2808-14. doi: 10.1016/j.bbamem.2013.04.019.
Site-2 proteases (S2Ps) are a class of intramembrane metalloproteases named after the founding member of this protein family, human S2P, which control cholesterol and fatty acid biosynthesis by cleaving Sterol Regulatory Element Binding Proteins which control cholesterol and fatty acid biosynthesis. S2Ps are widely distributed in bacteria and participate in diverse pathways that control such diverse functions as membrane integrity, sporulation, lipid biosynthesis, pheromone production, virulence, and others. The most common signaling mechanism mediated by S2Ps is the coupled degradation of transmembrane anti-Sigma factors to activate ECF Sigma factor regulons. However, additional signaling mechanisms continue to emerge as more prokaryotic S2Ps are characterized, including direct proteolysis of membrane embedded transcription factors and proteolysis of non-transcriptional membrane proteins or membrane protein remnants. In this review we seek to comprehensively review the functions of S2Ps in bacteria and bacterial pathogens and attempt to organize these proteases into conceptual groups that will spur further study. This article is part of a Special Issue entitled: Intramembrane Proteases.
2型位点蛋白酶（S2P）是一类膜内金属蛋白酶，以该蛋白家族的首个成员人类S2P命名，它通过切割控制胆固醇和脂肪酸生物合成的固醇调节元件结合蛋白来调控胆固醇和脂肪酸的生物合成。S2P广泛分布于细菌中，并参与多种途径，这些途径控制着诸如膜完整性、孢子形成、脂质生物合成、信息素产生、毒力等多种功能。S2P介导的最常见信号传导机制是跨膜抗西格玛因子的偶联降解，以激活ECF西格玛因子调控子。然而，随着越来越多的原核生物S2P被鉴定出来，其他信号传导机制也不断涌现，包括膜嵌入转录因子的直接蛋白水解以及非转录膜蛋白或膜蛋白残余物的蛋白水解。在本综述中，我们旨在全面回顾S2P在细菌和细菌病原体中的功能，并尝试将这些蛋白酶归类为概念性类别，以推动进一步研究。本文是名为“膜内蛋白酶”的特刊的一部分。
