BCL-2 family member BOK is widely expressed but its loss has only minimal impact in mice
BCL-2 family member BOK is widely expressed but its loss has only minimal impact in mice
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DOI：
10.1038/cdd.2011.210
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发表时间：
2012-06-01
影响因子：
12.4
通讯作者：
Kaufmann, T.
中科院分区：
文献类型：
--
作者：
Ke, F.;Voss, A.;Kaufmann, T.
BOK/MTD是一种结合抗凋亡Bcl-2家族成员MCL-1的蛋白，与BAX和BAK具有广泛的氨基酸序列相似性，这是细胞凋亡效应期所必需的。因此，基于其已报道的表达模式，我们认为BOK在女性生殖组织中以BAX/ bak样促凋亡的方式起作用。为了确定BOK的功能，我们检测了它在不同组织中的表达，并研究了它在BOK（-/-）小鼠中丢失的后果。我们证实Bok mRNA在卵巢和子宫中显著表达，但也观察到它在其他一些组织（如脑和髓细胞）中也以易于检测的水平存在。Bok（-/-）小鼠按预期的孟德尔比例繁殖，外观正常，并证明有生育能力。组织学检查显示，Bok（-/-）小鼠主要脏器未见形态学异常。虽然许多人类癌症都存在Bok基因的体细胞获得性拷贝数缺失，并且Bok在B淋巴样细胞中表达，但我们发现其缺失并不会加速E mu-Myc转基因小鼠的淋巴瘤发展。总之，这些结果表明，Bok可能在很大程度上与Bcl-2家族的其他成员的作用重叠，或者可能具有仅限于特定应激刺激和/或组织的功能。细胞死亡与分化（2012）19,915-925；doi: 10.1038 / cdd.2011.210;2012年1月27日在线发布
BOK/MTD was discovered as a protein that binds to the anti-apoptotic Bcl-2 family member MCL-1 and shares extensive amino-acid sequence similarity to BAX and BAK, which are essential for the effector phase of apoptosis. Therefore, and on the basis of its reported expression pattern, BOK is thought to function in a BAX/BAK-like pro-apoptotic manner in female reproductive tissues. In order to determine the function of BOK, we examined its expression in diverse tissues and investigated the consequences of its loss in Bok(-/-) mice. We confirmed that Bok mRNA is prominently expressed in the ovaries and uterus, but also observed that it is present at readily detectable levels in several other tissues such as the brain and myeloid cells. Bok(-/-) mice were produced at the expected Mendelian ratio, appeared outwardly normal and proved fertile. Histological examination revealed that major organs in Bok(-/-) mice displayed no morphological aberrations. Although several human cancers have somatically acquired copy number loss of the Bok gene and BOK is expressed in B lymphoid cells, we found that its deficiency did not accelerate lymphoma development in E mu-Myc transgenic mice. Collectively, these results indicate that Bok may have a role that largely overlaps with that of other members of the Bcl-2 family, or may have a function restricted to specific stress stimuli and/or tissues. Cell Death and Differentiation (2012) 19, 915-925; doi:10.1038/cdd.2011.210; published online 27 January 2012