Functional characterization of the Bcl-2 gene family in the zebrafish
Functional characterization of the Bcl-2 gene family in the zebrafish
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DOI：
10.1038/sj.cdd.4402016
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发表时间：
2006-10-01
影响因子：
12.4
通讯作者：
Ashkenazi, A.
中科院分区：
文献类型：
--
作者：
Kratz, E.;Eimon, P. M.;Ashkenazi, A.
Bcl-2蛋白家族的成员控制内在凋亡途径。为了评估这个家族在脊椎动物发育中的重要性，我们在斑马鱼（Danio rerio）中对其进行了研究。我们发现斑马鱼基因组编码大多数哺乳动物Bcl-2家族成员的结构和功能同源物，包括多Bcl-2同源（BH）结构域蛋白和BH 3-only蛋白。γ射线诱导的细胞凋亡需要zero 1和zPuma，并且可以通过过表达促生存Bcl-2家族成员的同源物来防止。令人惊讶的是，斑马鱼Bax 2（zerofish Bak 2）与哺乳动物Bax的序列和同线性同源，但与人类巴克的功能保守。Morpholino敲低zMcl-1a和zMcl-1b揭示了它们在早期胚胎斑马鱼发育中的关键作用，以及通过外源性途径调节凋亡激活。这些数据表明，斑马鱼和哺乳动物Bcl-2家族成员之间的功能相似性，并建立斑马鱼作为研究内源性凋亡途径的相关模型。
Members of the Bcl-2 protein family control the intrinsic apoptosis pathway. To evaluate the importance of this family in vertebrate development, we investigated it in the zebrafish (Danio rerio). We found that the zebrafish genome encodes structural and functional homologs of most mammalian Bcl-2 family members, including multi-Bcl-2-homology (BH) domain proteins and BH3-only proteins. Apoptosis induction by gamma-irradiation required zBax1 and zPuma, and could be prevented by overexpression of homologs of prosurvival Bcl-2 family members. Surprisingly, zebrafish Bax2 (zBax2) was homologous to mammalian Bax by sequence and synteny, yet demonstrated functional conservation with human Bak. Morpholino knockdown of both zMcl-1a and zMcl-1b revealed their critical role in early embryonic zebrafish development, and in the modulation of apoptosis activation through the extrinsic pathway. These data indicate substantial functional similarity between zebrafish and mammalian Bcl-2 family members, and establish the zebrafish as a relevant model for studying the intrinsic apoptosis pathway.