Huska Jason D, Lamb Heather M, Hardwick J Marie
Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Methods Mol Biol. 2019;1877:1-21. doi: 10.1007/978-1-4939-8861-7_1.
BCL-2 family proteins interact in a network that regulates apoptosis. The BH3 amino acid sequence motif serves to bind together this conglomerate protein family, both literally and figuratively. BH3 motifs are present in antiapoptotic and proapoptotic BCL-2 homologs, and in a separate group of unrelated BH3-only proteins often appended to the BCL-2 family. BH3-containing helices mediate many of their physical interactions to determine cell death versus survival, leading to the development of BH3 mimetics as therapeutics. Here we provide an overview of BCL-2 family interactions, their relevance in health and disease, and the progress toward regulating their interactions therapeutically.
BCL-2家族蛋白在一个调节细胞凋亡的网络中相互作用。BH3氨基酸序列基序在字面上和形象上都起到了将这个聚合蛋白家族结合在一起的作用。BH3基序存在于抗凋亡和促凋亡的BCL-2同源物中，以及经常附属于BCL-2家族的另一组不相关的仅含BH3的蛋白中。含BH3的螺旋介导了它们的许多物理相互作用，以决定细胞死亡还是存活，从而促成了BH3模拟物作为治疗药物的开发。在此，我们概述了BCL-2家族的相互作用、它们在健康和疾病中的相关性，以及在通过治疗调节它们的相互作用方面所取得的进展。
