Apoptosis is an important part of both health and disease and is often regulated by the BCL-2 family of proteins. These proteins are either pro- or anti-apoptotic, existing in a delicate balance during homeostasis. They are best known for their role in regulating the activation of caspases and the execution of a cell in response to a variety of stimuli. However, it is often forgotten that these BCL-2 family proteins also have important roles to play in cell maintenance that are not associated with apoptosis. These include roles in regulating processes such as cell cycle progression, mitochondrial function, autophagy, intracellular calcium concentration, glucose and lipid metabolism, and the unfolded protein response. In addition to these established alternate functions, further discoveries are being made that have potential therapeutic benefits in diseases such as cancer. BOK, a BCL-2 family protein thought comparable to multidomain pro-apoptotic proteins BAX and BAK, has recently been identified as a key player in metabolism of and resistance to the commonly used chemotherapeutic 5-FU. As a result of such findings, which could see the potential use of BOK as a biomarker for 5-FU sensitivity or mimetic molecules as a resensitization strategy, new targets and mechanisms of pathology may arise from further investigation into the realm of alternate functions of BCL-2 family proteins.

中文翻译：

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Bcl-2家族蛋白，超出面纱。

细胞凋亡是健康和疾病的重要组成部分，通常受BCL-2蛋白质家族的调节。这些蛋白质是促凋亡的或抗凋亡的，在稳态过程中以微妙的平衡存在。它们以在调节胱天蛋白酶激活和响应各种刺激的细胞执行中的作用而闻名。但是，通常会忘记这些BCL-2家族蛋白在与细胞凋亡无关的细胞维持中也起着重要作用。这些包括在调节过程中的作用，例如细胞周期进程，线粒体功能，自噬，细胞内钙浓度，葡萄糖和脂质代谢以及未折叠的蛋白质反应。除了这些已建立的替代功能之外，进一步发现对诸如癌症的疾病具有潜在的治疗益处。BOK是一种BCL-2家族蛋白，被认为可与多域促凋亡蛋白BAX和BAK媲美，最近被确定为常用化学疗法5-FU的代谢和耐药性的关键参与者。这些发现的结果是，BOK可能被用作5-FU敏感性的生物标志物或模拟分子作为再敏化策略的潜在用途，进一步研究BCL的替代功能领域可能会产生新的靶标和病理机制-2家族蛋白。最近已确定其为常用化学疗法5-FU的代谢和抗性的关键参与者。这些发现的结果是，BOK可能被用作5-FU敏感性的生物标志物或模拟分子作为再敏化策略的潜在用途，进一步研究BCL的替代功能领域可能会产生新的靶标和病理机制-2家族蛋白。最近已确定其为常用化学疗法5-FU的代谢和抗性的关键参与者。这些发现的结果是，BOK可能被用作5-FU敏感性的生物标志物或模拟分子作为再敏化策略的潜在用途，进一步研究BCL的替代功能领域可能会产生新的靶标和病理机制-2家族蛋白。