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  • CDC42 and Rac1 are implicated in the activation of the Nef-associated kinase and replication of HIV-1
    Lu, Xiaobin ...
    Backgraund: The negative factor (Nef) of human and simian immunodeficiency viruses (HIV-1, HIV-2 and SIV) is required for high levels of viremia and progression to AIDS. Additonally, Nef leads to ... cellualr activation, increased viral infectivity and decreased expression of CD4 on the cell surface. previously, we and others demonstrated that Nef associates with a cellular serine kinase (NAK) activity. Recently, it was demonstrated that NAK bears structural and functional similarity to p21-activated kinases (PAKs). Results:In this study, we demonstrate that Nef not only binds to but also activates NAK via the small GTPases CDC42 and Rac1. First, the dominant-negative PAK (PAKR), via its GTPase-binding domain, and dominant-negative PAK (PAKR), via its GTPase-binding domain, and dominant-negative GTPases (CDC42Hs-N17 and Rac1-N17) block the ability of Nef to associate with and activate NAK. Second, constitutively active small GTPases (CDC42Hs-V12 and Rac1-V12) potentiate the effects of Nef. Third, interactions between Nef and NAK result in several cellular effector functions, such as activation of the serum-response pathway. And finally, PAKR, CDC42Hs-N17 and Rac1-N17 decrease levels of HIV-1 production to those ofvirus from which the nef gene is deleted. Conclusions: By activating NAK viasmall GTPases and their downstream effectors, Nef interacts with regulatorypathways required for cell growth, cytoskeletal rearrangement and andocytosis. Thus, NAK could participate in the budding of new virions, the modification of viral proteins and the increased endocytosis of surface molecules such as CD4. Moreover, blocking the activity of these GTPases could lead to new therapeutic interventions against AIDS.
    Source: Current biology. - ISSN 0960-9822 (Let. 6, št. 12, 1996, str. 1677-1684)
    Type of material - article, component part
    Publish date - 1996
    Language - english
    COBISS.SI-ID - 165337

source: Current biology. - ISSN 0960-9822 (Let. 6, št. 12, 1996, str. 1677-1684)
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