Coultas L, Pellegrini M, Visvader J E, Lindeman G J, Chen L, Adams J M, Huang D C S, Strasser A
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Cell Death Differ. 2003 Feb;10(2):185-92. doi: 10.1038/sj.cdd.4401204.
Proteins of the Bcl-2 family are critical regulators of apoptosis. Proapoptotic members, like Bax, contain three of the four Bcl-2 homology regions (BH1-3), while BH3-only proteins, like Bim, possess only the short BH3 motif. Database searches revealed Bfk, an unusual novel member of the Bcl-2 family that contains a BH2 and BH3 region but not BH1 or BH4. Bfk is thus most closely related to Bcl-G(L). It lacks a C-terminal membrane anchor and is cytosolic. Enforced expression of Bfk weakly promoted apoptosis and antagonized Bcl-2's prosurvival function. Like Bcl-G(L), Bfk did not bind to any Bcl-2 family members, even though its BH3 motif can mediate association with prosurvival proteins. Low amounts of Bfk were found in stomach, ovary, bone marrow and spleen, but its level in the mammary gland rose markedly during pregnancy, suggesting that Bfk may play a role in mammary development.
Bcl-2家族蛋白是细胞凋亡的关键调节因子。促凋亡成员,如Bax,包含四个Bcl-2同源区域(BH1-3)中的三个,而仅含BH3结构域的蛋白,如Bim,仅拥有短的BH3基序。数据库搜索发现了Bfk,它是Bcl-2家族中一个不同寻常的新成员,含有BH2和BH3区域,但不含BH1或BH4。因此,Bfk与Bcl-G(L)关系最为密切。它缺乏C末端膜锚定结构,位于胞质中。Bfk的强制表达微弱地促进细胞凋亡,并拮抗Bcl-2的促生存功能。与Bcl-G(L)一样,Bfk不与任何Bcl-2家族成员结合,尽管其BH3基序可介导与促生存蛋白的结合。在胃、卵巢、骨髓和脾脏中发现少量的Bfk,但其在乳腺中的水平在妊娠期间显著升高,表明Bfk可能在乳腺发育中发挥作用。