HIV-1 incorporates and proteolytically processes human NDR1 and NDR2 serine-threonine kinases
HIV-1 incorporates and proteolytically processes human NDR1 and NDR2 serine-threonine kinases
复制标题
DOI：
10.1016/j.virol.2004.10.023
复制
发表时间：
2005-01-05
期刊：
影响因子：
3.7
通讯作者：
Engelman, A
中科院分区：
文献类型：
--
作者：
Devroe, E;Silver, PA;Engelman, A
哺乳动物基因组编码两种相关的丝氨酸-苏氨酸激酶，核Dbf 2相关（NDR）1和NDR 2，它们与酿酒酵母Dbf 2激酶同源。最近，一个酵母遗传筛选牵连Dbf 2激酶在Ty 1逆转录转座。由于几种病毒体掺入激酶调节人类免疫缺陷病毒1型（HIV-1）的感染性，我们推测，人NDR 1和NDR 2激酶可能在HIV-1的生命周期中发挥作用。在这里，我们表明，NDR 1和NDR-2激酶被纳入HIV-1颗粒。此外，NDR 1和NDR 2被HIV-1蛋白酶（PR）切割。无论是在病毒体内还是在生产细胞内。PR切割位点的截断改变了NDR 2的亚细胞定位，并抑制了NDR 1和NDR 2的酶活性。这些研究确定了两种新的病毒体相关的宿主细胞酶，并提出了一种新的机制，HIV-1改变了人类细胞的细胞内环境。(C)2004年爱思唯尔公司All rights reserved.
Mammalian genomes encode two related serine-threonine kinases, nuclear Dbf2 related (NDR)1 and NDR2, which are homologous to the Saccharomyces cerevisiae Dbf2 kinase. Recently, a yeast genetic screen implicated the Dbf2 kinase in Ty1 retrotransposition. Since several virion-incorporated kinases regulate the infectivity of human immunodeficiency virus type 1 (HIV-1), we speculated that the human NDR1 and NDR2 kinases might play a role in the HIV-1 life cycle. Here we show that the NDR1 and NDR-2 kinase were incorporated into HIV-1 particles. Furthermore, NDR1 and NDR2 were cleaved by the HIV-1 protease (PR). both within virions and within producer cells. Truncation at the PR cleavage site altered NDR2 subcellular localization and inhibited NDR1 and NDR2 enzymatic activity. These studies identify two new virion-associated host cell enzymes and suggest a novel mechanism by which HIV-1 alters the intracellular environment of human cells. (C) 2004 Elsevier Inc. All rights reserved.