Emerging understanding of Bcl-2 biology: Implications for neoplastic progression and treatment.
Emerging understanding of Bcl-2 biology: Implications for neoplastic progression and treatment.
复制标题
对BCL-2生物学的新兴理解：对肿瘤进展和治疗的影响。
DOI：
10.1016/j.bbamcr.2015.03.012
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发表时间：
2015-07
影响因子：
5.1
通讯作者：
Kaufmann, Scott H.
中科院分区：
文献类型：
--
作者：
Correia, Cristina;Lee, Sun-Hee;Meng, X. Wei;Vincelette, Nicole D.;Knorr, Katherine L. B.;Ding, Husheng;Nowakowski, Grzegorz S.;Dai, Haiming;Kaufmann, Scott H.
Bcl-2是凋亡调节因子家族的创始成员，最初被鉴定为在超过85%的滤泡性淋巴瘤（FL）中易位和过表达的基因的蛋白产物。30年后，我们现在了解到Bcl-2通过结合和中和线粒体透化剂Bax和巴克以及各种促凋亡蛋白，包括细胞应激传感器Bim、Bid、Puma、Bad、Bmf以及在某些条件下的Noxa，来调节内在凋亡途径。尽管对所有这些蛋白质进行了广泛的研究，但仍然存在重要的问题。例如，Bax和巴克如何突破线粒体外膜仍然知之甚少。同样地，抗凋亡Bcl-2家族成员如表位Bcl-2的功能如何受到磷酸化或癌症相关突变的影响也没有完全确定。最后，Bcl-2家族成员是否可以成功地靶向治疗优势，现在只是在临床上进行调查。在这里，我们回顾了最近的进展，了解Bcl-2家族的生物学和生物化学，开始解决这些问题。
Bcl-2, the founding member of a family of apoptotic regulators, was initially identified as the protein product of a gene that is translocated and overexpressed in greater than 85% of follicular lymphomas (FLs). Thirty years later we now understand that Bcl-2 modulates the intrinsic apoptotic pathway by binding and neutralizing the mitochondrial permeabilizers Bax and Bak as well as a variety of pro-apoptotic proteins, including the cellular stress sensors Bim, Bid, Puma, Bad, Bmf and, under some conditions, Noxa. Despite extensive investigation of all of these proteins, important questions remain. For example, how Bax and Bak breach the outer mitochondrial membrane remains poorly understood. Likewise, how the functions of anti-apoptotic Bcl-2 family members such as eponymous Bcl-2 are affected by phosphorylation or cancer-associated mutations has been incompletely defined. Finally, whether Bcl-2 family members can be successfully targeted for therapeutic advantage is only now being investigated in the clinic. Here we review recent advances in understanding Bcl-2 family biology and biochemistry that begin to address these questions.
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