The apoptosis pathway triggered by the interferon-induced protein kinase PKR requires the third basic domain, initiates upstream of Bcl-2, and involves ICE-like proteases
The apoptosis pathway triggered by the interferon-induced protein kinase PKR requires the third basic domain, initiates upstream of Bcl-2, and involves ICE-like proteases
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DOI：
10.1006/viro.1997.8494
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发表时间：
1997-04-28
期刊：
影响因子：
3.7
通讯作者：
Esteban, M
中科院分区：
文献类型：
--
作者：
Lee, SB;Rodriguez, D;Esteban, M
干扰素诱导的双链RNA依赖蛋白激酶(PKR)是一种丝氨酸/苏氨酸激酶，具有抗病毒和抗细胞功能。PKR的抗病毒作用是通过翻译起始因子ELF-2α的α亚基的磷酸化来实现的，目前尚不清楚这种抗细胞作用是由于ELF-2α、L kappa B或其他未知底物的磷酸化所致。我们以前已经证明，在表达野生型激酶的痘苗病毒重组体感染细胞期间，PKR的激活导致病毒和细胞蛋白质合成的完全抑制，并诱导细胞凋亡。在这里，我们报告了人类原癌基因bcl2的表达可以阻止PKR诱导的细胞凋亡，但不能阻止PKR诱导的翻译抑制。此外，PKR诱导的细胞凋亡导致死亡底物多聚(ADP-核糖)聚合酶(PARP)的裂解。此外，在缺失第三碱基区的突变体(AA 234-272)中，未观察到PKR诱导的细胞凋亡。综上所述，这些结果表明，PKR的第三个碱基区是PKR诱导细胞凋亡所必需的，这一过程始于bcl2上游，涉及到裂解PARP的细胞蛋白酶CPP32或其家族成员的激活。(C)1997年学术出版社。
The interferon-induced double-stranded RNA-dependent protein kinase (PKR) is a serine/threonine kinase which exerts antiviral and anticellular functions. The antiviral effect of PKR is mediated by the phosphorylation of the alpha subunit of the translational initiation factor elF-2 alpha it is not known whether the anticellular effect is due to phosphorylation of elF-2 alpha, l kappa B, or other unknown substrates. We have previously shown that activation of PKR during infection of cells with a vaccinia virus recombinant expressing the wild-type kinase resulted in a complete inhibition of viral and cellular protein synthesis and in the induction of apoptosis. Here, we report that expression of the human proto-oncogene bcl-2 blocks PKR-induced apoptosis but not PKR-induced inhibition of translation. In addition, PKR-induced apoptosis resulted in a cleavage of the death substrate poly(ADP-ribose) polymerase (PARP). Moreover, induction of apoptosis by PKR was not observed with a mutant lacking the third basic region (aa 234-272). Taken together, these results suggest that the third basic region of PKR is required for PKR-induced apoptosis, the process is initiated upstream of bcl-2 and involves activation of a cellular protease, CPP32, or its family members that cleave PARP. (C) 1997 Academic Press.