The E1B 19K protein blocks apoptosis by interacting with and inhibiting the p53-inducible and death-promoting Bax protein
The E1B 19K protein blocks apoptosis by interacting with and inhibiting the p53-inducible and death-promoting Bax protein
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DOI：
10.1101/gad.10.4.461
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发表时间：
1996-02-15
影响因子：
10.5
通讯作者：
White, E
中科院分区：
文献类型：
--
作者：
Han, JH;Sabbatini, P;White, E
E1B 19K 蛋白是一种有效的细胞凋亡抑制剂，也是假定的腺病毒 Bcl-2 同源物。为了研究细胞凋亡调节机制，使用酵母双杂交系统鉴定了 19K 相互作用细胞蛋白，Bax 是七个 19K 相互作用克隆之一。 Bax 的残基 50-78 含有称为 Bcl-2 同源区 3 (BH3) 的保守区，足以特异性结合 E1B 19K 和 Bcl-2 蛋白。 Bax-E1B 19K 相互作用在体外和哺乳动物细胞裂解物中均可检测到，并且 Bax 表达会拮抗 E1B 19K 蛋白功能。 box mRNA 和蛋白水平是 p53 诱导的，其动力学与 p21/Waf-1/Cip-1 相同，并且 E1B 19K 和 Bcl-2 表达不影响 Bax 或 p21/Waf-1/Cip-1 积累。在 p53 突变的细胞中，Bax 表达诱导细胞凋亡，表明 Bax 足以促进细胞凋亡，并在 p53 下游发挥作用。 p53 可能同时激活生长停滞 (p21/Waf-1/Cip-1) 和死亡所需基因的转录（方框），E1B 19K 和 Bcl-2 可能在远端发挥作用，并通过与 Bax 相互作用和拮抗发挥作用，以防止细胞凋亡。当死亡途径被禁用时，p53 诱导的生长停滞就会显现出来。
The E1B 19K protein is a potent apoptosis inhibitor and the putative adenovirus Bcl-2 homolog. To investigate the mechanism of apoptosis regulation, 19K-interacting cellular proteins were identified using the yeast two-hybrid system, and Bax was one of seven 19K-interacting clones. Residues 50-78 of Bax containing a conserved region designated Bcl-2 homology region 3 (BH3) were sufficient for specific binding to both the E1B 19K and Bcl-2 proteins. The Bax-E1B 19K interaction was detectable in vitro and in lysates from mammalian cells, and Bax expression antagonized E1B 19K protein function. box mRNA and protein levels were p53-inducible with kinetics identical to that of p21/Waf-1/Cip-1, and E1B 19K and Bcl-2 expression did not affect Bax or p21/Waf-1/Cip-1 accumulation. In cells where p53 was mutant, Bax expression induced apoptosis, suggesting that Bax was sufficient for apoptosis, and acted downstream of p53. p53 may simultaneously activate the transcription of genes required for both growth arrest (p21/Waf-1/Cip-1) and death (box), and E1B 19K and Bcl-2 may act distally and function through interaction with and antagonism of Bax to prevent apoptosis. With the death pathway disabled, induction of growth arrest by p53 can then be manifested.