Siddiqui Waseem Ahmad, Ahad Amjid, Ahsan Haseeb
Department of Biochemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
Arch Toxicol. 2015 Mar;89(3):289-317. doi: 10.1007/s00204-014-1448-7. Epub 2015 Jan 25.
Apoptosis is a critically important biological process that plays an essential role in cell fate and homeostasis. An important component of the apoptotic pathway is the family of proteins commonly known as the B cell lymphoma-2 (Bcl-2). The primary role of Bcl-2 family members is the regulation of apoptosis. Although the structure of Bcl-2 family of proteins was reported nearly 10 years ago, however, it still surprises us with its structural and functional complexity and diversity. A number of studies have demonstrated that Bcl-2 family influences many other cellular processes beyond apoptosis which are generally independent of the regulation of apoptosis, suggesting additional roles for Bcl-2. The disruption of the regulation of apoptosis is a causative event in many diseases. Since the Bcl-2 family of proteins is the key regulator of apoptosis, the abnormalities in its function have been implicated in many diseases including cancer, neurodegenerative disorders, ischemia and autoimmune diseases. In the past few years, our understanding of the mechanism of action of Bcl-2 family of proteins and its implications in various pathological conditions has enhanced significantly. The focus of this review is to summarize the current knowledge on the structure and function of Bcl-2 family of proteins in apoptotic cellular processes. A number of drugs have been developed in the past few years that target different Bcl-2 members. The role of Bcl-2 proteins in the pathogenesis of various diseases and their pharmacological significance as effective molecular therapeutic targets is also discussed.
细胞凋亡是一个至关重要的生物学过程，在细胞命运和内环境稳态中发挥着关键作用。凋亡途径的一个重要组成部分是通常被称为B细胞淋巴瘤-2（Bcl-2）的蛋白质家族。Bcl-2家族成员的主要作用是调节细胞凋亡。尽管Bcl-2蛋白质家族的结构在近10年前就已被报道，然而，其结构和功能的复杂性与多样性仍然令我们感到惊讶。许多研究表明，Bcl-2家族除了影响细胞凋亡外，还会影响许多其他细胞过程，这些过程通常独立于细胞凋亡的调节，这表明Bcl-2还有其他作用。细胞凋亡调节的破坏是许多疾病的致病因素。由于Bcl-2蛋白质家族是细胞凋亡的关键调节因子，其功能异常与包括癌症、神经退行性疾病、缺血和自身免疫性疾病在内的许多疾病有关。在过去几年中，我们对Bcl-2蛋白质家族的作用机制及其在各种病理状况中的意义的理解有了显著提高。本综述的重点是总结目前关于Bcl-2蛋白质家族在凋亡细胞过程中的结构和功能的知识。在过去几年中，已经开发出了许多针对不同Bcl-2成员的药物。还讨论了Bcl-2蛋白质在各种疾病发病机制中的作用及其作为有效分子治疗靶点的药理学意义。
