一种新的Bax异构体Baxθ促进细胞凋亡(英文)  

Baxθ,a Novel Bax Variant,Lacks BH3 Domain and Promotes Cell Apoptosis

作　　者：许正新[1,2] 王瑧瑧[1] 王然[1] 谢林俊[1,2] 薛京伦[1] 陈金中[1] 

机构地区：[1]复旦大学生命科学学院遗传学研究所遗传工程国家重点实验室,上海200433 [2]扬州大学医学院药学系,扬州225001

出　　处：《复旦学报（自然科学版）》2014年第3期321-328,共8页Journal of Fudan University：Natural Science

基　　金：the National Natural Science Foundation of China(31071171,801170532);the National Basic Research Program of China(2010CB529903)

摘　　要：Bcl-2蛋白家族由一类含有特征性的Bcl-2同源结构BH、且主要调控细胞死亡的蛋白组成．Bax是一个含有多个特征性BH结构域、促进凋亡的蛋白．克隆了一个全新的Bax异构体Baxθ其eDNA由外显子1，4，5，6组成．MTC表达谱分析显示Baxθ在人体各组织中广泛且不同强度的表达．将Baxθ ORF插入pEGFP-N1载体，转染HEK293细胞，观察到一个15ku的融合蛋白，提示Baxθ编码的蛋白是与Baxβ共用同一个C端，且使用一个全新的翻译起始位点．尽管Baxθ缺乏BH3结构域，但它在HEK293细胞中过表达时能促进细胞凋亡．截断体实验分析发现Baxθ第43～69位氨基酸残基可能与其促进细胞凋亡的活性有关．BH3结构域可能不是Bel-2蛋白家族诱导细胞凋亡的唯一功能区域．Abstract： Proteins of the Bcl-2 family are major regulators of programmed cell death and characterized by up to four Bcl-2 homology domains. Bax is a multidomain proapoptotie protein which serves as the gateway to apoptosis. We identified a novel eDNA of Bax, namely Baxθ, which consists of exon 1, 4, 5, 6 comparing to classic Baxβ. The multiple tissue eDNA（MTC） based expression pattern assay revealed that Baxθ was ubiquitously expressed in human tissues with different intensity. The eDNA of Baxθ was inserted into pEGFP-N1 and then transfected HEK293 cells. In the result, a 15 ku fusion protein was detected, suggesting that Baxθ encodes a putative protein which shares the same C-terminus with Baxβ using a novel initiating translation ATG. Protein Baxθ could trigger strong apoptosis when it was overexpressed in HEK293 cells though it lacks BH3 domain. Further, the deletion assay indicated that 43--69 residues of Baxθ played an essential role in its proapoptotie activity. BH3 domain may not be the only function unit for inducing apoptosis in Bel-2 family proteins.

关 键 词：BAX 异构体 细胞凋亡 

分 类 号：Q51[生物学—生物化学]