HIV-1 incorporates and proteolytically processes human NDR1 and NDR2 serine-threonine kinases |
| |
Authors: | Devroe Eric Silver Pamela A Engelman Alan |
| |
Institution: | Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. |
| |
Abstract: | 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 NDR2 kinases 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. |
| |
Keywords: | NDR nuclear Dbf2 related HIV-1 human immunodeficiency virus type 1 PR protease WT wild type CA capsid CIP calf intestinal alkaline phosphatase C-PKA cAMP-dependent protein kinase DMSO dimethyl sulfoxide GFP green fluorescent protein PMSF phenylmethylsulfonyl fluoride NP-40 Nonidet P40 SDS sodium dodecyl sulfate EDTA ethylenediaminetetraacetic acid |
本文献已被 ScienceDirect PubMed 等数据库收录! |