BOD (Bcl-2-Related ovarian death gene) is an ovarian BH3 domain-containing proapoptotic Bcl-2 protein capable of dimerization with diverse antiapoptotic Bcl-2 members
BOD (Bcl-2-Related ovarian death gene) is an ovarian BH3 domain-containing proapoptotic Bcl-2 protein capable of dimerization with diverse antiapoptotic Bcl-2 members
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DOI：
10.1210/me.12.9.1432
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发表时间：
1998-09-01
影响因子：
--
通讯作者：
Hsueh, AJW
中科院分区：
文献类型：
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作者：
Hsu, SY;Lin, P;Hsueh, AJW
利用酵母双杂交蛋白-蛋白相互作用系统寻找能够与抗凋亡蛋白Mcl-1形成二聚体的基因，我们从卵巢融合基因文库中分离到BOD(BOD)。BOD的三个变异体(长、中、短)分别有一个由196、110和93个氨基酸组成的开放阅读框架；它们都含有共同的BH3结构域，但缺乏通道形成蛋白中的其他BH结构域。在酵母细胞实验中，BOD与不同的抗凋亡蛋白[Mcl-1、Bcl2、Bclxl、Bclw、Bfl-1和EB病毒(EBV)BHRF-1]相互作用，但不与不同的促凋亡蛋白(Bad、Bak、Bok和Bar)相互作用。BOD在哺乳动物中国仓鼠卵巢(CHO)细胞中过表达后，可诱导细胞凋亡，这可被杆状病毒caspase抑制剂P35阻止。BOD的细胞杀伤活性在与抗细胞凋亡蛋白共转染的细胞中也被拮抗，在双杂交实验中显示出与BOD的高亲和力。此外，诱变研究表明，BH3结构域改变的BOD突变体失去了杀伤细胞的能力，这表明BH3结构域在BOD介导细胞杀伤过程中起着重要作用。BOD基因在卵巢等多种组织中广泛表达。BOD基因在不同的哺乳动物物种中也是保守的。BOD的鉴定扩大了只含有BH3结构域的促凋亡蛋白的范围，并使未来能够阐明卵巢和其他组织中细胞内调控细胞凋亡的机制。
Using the yeast two-hybrid protein-protein interaction system to search for genes capable of forming dimers with the antiapoptotic protein Mcl-1, we have isolated BOD (Bcl-2-related ovarian death agonist) from an ovarian fusion cDNA library. The three variants of BOD (long, medium, and short) have an open reading frame of 196, 110, and 93 amino acids, respectively; all of them contain a consensus Bcl-2 homology 3 (BH3) domain but lack other BH domains found in channel-forming Bcl-2 family proteins. In the yeast cell assay, BOD interacts with diverse antiapoptotic Bcl-2 proteins [Mcl-1, Bcl-2, Bcl-xL, Bcl-w, Bfl-1, and Epstein-Barr virus (EBV) BHRF-1] but not with different proapoptotic Bcl-2 proteins (BAD, Bak, Bok, and Bar). After overexpression in mammalian Chinese hamster ovary (CHO) cells, BOD induces apoptosis that can be prevented by the baculoviral caspase inhibitor P35. The cell-killing activity of BOD is also antagonized in cells cotransfected with the antiapoptotic Bcl-w protein, which showed high affinity for BOD in the two-hybrid assay. Furthermore, mutagenesis studies showed that BOD mutants with alterations in the BH3 domain lose cell-killing ability, suggesting that the BH3 domain is important for the mediation of cell killing by BOD. BOD mRNA is ubiquitously expressed in ovary and multiple other tissues. The BOD gene is also conserved in diverse mammalian species. Identification of BOD expands the group of proapoptotic Bcl-2 proteins that only contains the BH3 domain and allows future elucidation of the intracellular mechanism for apoptosis regulation in ovary and other tissues.