A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak
A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak
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DOI：
10.1073/pnas.94.2.690
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发表时间：
1997-01-21
影响因子：
11.1
通讯作者：
Hardwick, JM
中科院分区：
文献类型：
--
作者：
Cheng, EHY;Nicholas, J;Hardwick, JM
Bcl-2蛋白家族的特点是具有调节细胞死亡的能力，该家族的成员共享两个高度保守的结构域，称为Bcl-2同源1 （BH1）和2 (BH2)，这两个结构域已被证明对Bcl-2和Bcl-x(L)的死亡抑制活性至关重要。通过序列分析，我们从人类疱疹病毒8 （HHV8）或卡波西肉瘤相关疱疹病毒中鉴定出一种新的病毒Bcl-2同源物，命名为KSbcl-2。KSbcl-2与其他Bcl-2同源物之间的氨基酸序列总体一致性较低（15-20%），但集中在BH1和BH2区域。KSbcl-2的过表达与Bcl-2、Bcl-x(L)或另一种由eb病毒编码的Bcl-2同源物BHRF1一样有效地阻断细胞凋亡。有趣的是，KSbcl-2既不与其他Bcl-2家族成员同质二聚，也不与其他Bcl-2家族成员异源二聚，这表明KSbcl-2可能已经进化到逃避细胞Bax和Bah蛋白的任何负面调节作用。此外，与其他哺乳动物的Bcl-2同源物相比，猴猴疱疹病毒的Bcl-2同源物包括KSbcl-2、BHRF1和ORF16含有保守性较差的Bcl-2同源3 （BH3）结构域，这意味着BH3可能不是抗凋亡功能所必需的。这与我们的观察一致，即Bcl-x(L)的BH3结构域内的氨基酸替换对其死亡抑制活性没有影响。
The Bcl-2 protein family is characterized by the ability to modulate cell death, and members of this family share two highly conserved domains called Bcl-2 homology 1 (BH1) and 2 (BH2) which have been shown to be critical for the death-repressor activity of Bcl-2 and Bcl-x(L). Through sequence analysis we identified a novel viral Bcl-2 homolog, designated KSbcl-2, from human herpesvirus 8 (HHV8) or Kaposi sarcoma-associated herpesvirus. The overall amino acid sequence identity between KSbcl-2 and other Bcl-2 homologs is low (15-20%) but concentrated within the BH1 and BH2 regions. Overexpression of KSbcl-2 blocked apoptosis as efficiently as Bcl-2, Bcl-x(L), or another viral Bcl-2 homolog encoded by Epstein-Barr virus, BHRF1. Interestingly, KSbcl-2 neither homodimerizes nor heterodimerizes with other Bcl-2 family members, suggesting that KSbcl-2 may have evolved to escape any negative regulatory effects of the cellular Bax and Bah proteins. Furthermore, the herpesvirus Bcl-2 homologs including KSbcl-2, BHRF1, and ORF16 of herpesvirus saimiri contain poorly conserved Bcl-2 homology 3 (BH3) domains compared with other mammalian Bcl-2 homologs, implying that BH3 may not be essential for anti-apoptotic function. This is consistent with our observation that amino acid substitutions within the BH3 domain of Bcl-x(L) had no effect on its death suppressor activity.