title: HIV-1 incorporates and proteolytically processes human NDR1 and NDR2 serine-threonine kinases.
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.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Devroe
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Silver
authors.forename: Alan
authors.initials: A
authors.lastname: Engelman
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D016333:HIV Protease / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014771:Virion
chemical_list: D017346:Protein Serine-Threonine Kinases; C491614:STK38 protein, human; C496014:STK38L protein, human; D016333:HIV Protease