Department of Molecular Biology of Cancer, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215, Lodz, Poland.
Cell Death Dis. 2020 Apr 21;11(4):260. doi: 10.1038/s41419-020-2417-0.
The BCL-2 family of proteins integrates signals that trigger either cell survival or apoptosis. The balance between pro-survival and pro-apoptotic proteins is important for tissue development and homeostasis, while impaired apoptosis contributes to several pathologies and can be a barrier against effective treatment. BCL-w is an anti-apoptotic protein that shares a sequence similarity with BCL-X, and exhibits a high conformational flexibility. BCL-w level is controlled by a number of signaling pathways, and the repertoire of transcriptional regulators largely depends on the cellular and developmental context. As only a few disease-relevant genetic alterations of BCL2L2 have been identified, increased levels of BCL-w might be a consequence of abnormal activation of signaling cascades involved in the regulation of BCL-w expression. In addition, BCL-w transcript is a target of a plethora of miRNAs. Besides its originally recognized pro-survival function during spermatogenesis, BCL-w has been envisaged in different types of normal and diseased cells as an anti-apoptotic protein. BCL-w contributes to survival of senescent and drug-resistant cells. Its non-apoptotic role in the promotion of cell migration and invasion has also been elucidated. Growing evidence indicates that a high BCL-w level can be therapeutically relevant in neurodegenerative disorders, neuron dysfunctions and after small intestinal resection, whereas BCL-w inhibition can be beneficial for cancer patients. Although several drugs and natural compounds can bi-directionally affect BCL-w level, agents that selectively target BCL-w are not yet available. This review discusses current knowledge on the role of BCL-w in health, non-cancerous diseases and cancer.
BCL-2 蛋白家族整合了触发细胞存活或凋亡的信号。促生存和促凋亡蛋白之间的平衡对于组织发育和内稳态很重要，而凋亡受损会导致多种病理，并可能成为有效治疗的障碍。BCL-w 是一种抗凋亡蛋白，与 BCL-X 具有序列相似性，并且表现出高度的构象灵活性。BCL-w 的水平受许多信号通路的控制，转录调节剂的 repertoire 在很大程度上取决于细胞和发育背景。由于仅鉴定出少数与 BCL2L2 相关的疾病相关遗传改变，因此 BCL-w 的水平升高可能是参与 BCL-w 表达调控的信号级联异常激活的结果。此外，BCL-w 转录本是众多 miRNAs 的靶标。除了在精子发生过程中最初被认为具有促生存功能外，BCL-w 还被设想为正常和患病细胞中的抗凋亡蛋白。BCL-w 有助于衰老和耐药细胞的存活。它在促进细胞迁移和侵袭中的非凋亡作用也已阐明。越来越多的证据表明，高 BCL-w 水平在神经退行性疾病、神经元功能障碍和小肠切除后可能具有治疗相关性，而 BCL-w 抑制对癌症患者可能有益。尽管几种药物和天然化合物可以双向影响 BCL-w 水平，但尚未有专门针对 BCL-w 的药物。本文综述了 BCL-w 在健康、非癌症疾病和癌症中的作用的最新知识。
