BCL-w：在健康和疾病中具有凋亡和非凋亡作用。,Cell Death & Disease

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BCL-w：在健康和疾病中具有凋亡和非凋亡作用。
Cell Death & Disease ( IF 8.1 ) Pub Date : 2020-04-21 , DOI: 10.1038/s41419-020-2417-0
Mariusz L Hartman ₁ , Malgorzata Czyz ₁

Affiliation

BCL-2蛋白家族整合了触发细胞存活或凋亡的信号。促生存蛋白和促凋亡蛋白之间的平衡对于组织发育和体内平衡很重要，而凋亡受损会导致多种病理，并且可能成为有效治疗的障碍。BCL-w是一种抗凋亡蛋白，与BCL-XL具有序列相似性，并具有很高的构象柔韧性。BCL-w水平受许多信号传导途径控制，转录调节因子的组成在很大程度上取决于细胞和发育环境。由于仅发现了少数与疾病相关的BCL2L2基因改变，因此BCL-w水平升高可能是参与BCL-w表达调节的信号级联反应异常激活的结果。此外，BCL-w转录物是大量miRNA的靶标。除了在生精过程中最初公认的促生存功能外，BCL-w还被认为是在不同类型的正常和患病细胞中作为抗凋亡蛋白。BCL-w有助于衰老和耐药细胞的存活。还阐明了其在促进细胞迁移和侵袭中的非凋亡作用。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术后可能与治疗相关，而BCL-w抑制可能对癌症患者有益。尽管几种药物和天然化合物可以双向影响BCL-w的水平，但尚无选择性靶向BCL-w的药物。这篇评论讨论了有关BCL-w在健康中的作用的最新知识，

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BCL-w: apoptotic and non-apoptotic role in health and disease.

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-XL, 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.

更新日期：2020-04-24

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