Bcl-G, a novel pro-apoptotic member of the Bcl-2 family
Bcl-G, a novel pro-apoptotic member of the Bcl-2 family
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DOI：
10.1074/jbc.m005889200
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发表时间：
2001-01-26
影响因子：
4.8
通讯作者：
Reed, JC
中科院分区：
文献类型：
--
作者：
Guo, B;Godzik, A;Reed, JC
Bcl-2家族的一个新成员Bcl-G基因位于染色体12 p12，由6个外显子组成，通过mRNA选择性剪接编码两个蛋白质，Bcl-G（L）（长）和Bcl-G（S）（短），分别由327和252个氨基酸组成。Bcl-G（L）和Bcl-G（S）的前226个氨基酸具有相同的序列，但之后不同。在以前在Bcl-2家族蛋白中识别的Bcl-2同源（BH）结构域中，BH 3结构域在Bcl-G（L）和Bcl-G（S）中均被发现，但只有较长的Bcl-G（L）蛋白具有BH 2结构域。Bcl-G（L）mRNA在成人组织中广泛表达，而Bcl-G（S）mRNA仅在睾丸中表达。Bcl-G（S）和Bcl-G（L）的过表达均能诱导细胞凋亡，但Bcl-G（S）的诱导凋亡作用远强于Bcl-G（L），Bcl-G（S）的诱导凋亡作用依赖于BH 3结构域，并被抗凋亡蛋白Bcl-X-L的共表达所抑制。Bcl-X-L也与Bcl-G（S）免疫共沉淀，但不与Bcl-G（S）的突变体（其中BH 3结构域缺失或突变）或Bcl-G（L）免疫共沉淀。Bcl-G（S）主要定位于胞质细胞器，而Bcl-G（L）则弥漫分布于整个胞质。Bcl-G（L）的突变体中BH 2结构域被删除，表现出增加的凋亡活性，并与Bcl-X-L共免疫沉淀，表明BH 2结构域自身抑制Bcl-G（L）。
A new member of the Bcl-2 family was identified, Bcl-G, The human BCL-G gene consists of 6 exons, resides on chromosome 12p12, and encodes two proteins through alternative mRNA splicing, Bcl-G(L) (long) and Bcl-G(S) (short) consisting of 327 and 252 amino acids in length, respectively. Bcl-G(L) and Bcl-G(S) have identical sequences for the first 226 amino acids but diverge thereafter. Among the Bcl-2 homology (BH) domains previously recognized in Bcl-2 family proteins, the BH3 domain is found in both Bcl-G(L) and Bcl-G(S), but only the longer Bcl-G(L) protein possesses a BH2 domain. Bcl-G(L) mRNA is expressed widely in adult human tissues, whereas Bcl-G(S) mRNA was found only in testis. Overexpression of Bcl-G(L) or Bcl-G(S) in cells induced apoptosis although Bcl-G(S) was far more potent than Bcl-G(L), Apoptosis induction by Bcl-G(S) depended on the BH3 domain and was suppressed by coexpression of anti-apoptotic Bcl-X-L protein. Bcl-X-L also coimmunoprecipitated with Bcl-G(S) but not with mutants of Bcl-G(S) in which the BH3 domain was deleted or mutated or with Bcl-G(L). Bcl-G(S) was predominantly localized to cytosolic organelles, whereas Bcl-G(L) was diffusely distributed throughout the cytosol. A mutant of Bcl-G(L) in which the BH2 domain was deleted displayed increased apoptotic activity and coimmunoprecipitated with Bcl-X-L, suggesting that the BH2 domain autorepresses Bcl-G(L).