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HIV-1 Tat directly interacts with the interferon-induced, double-stranded RNA-dependent kinase, PKR.
McMillan, N A; Chun, R F; Siderovski, D P; Galabru, J; Toone, W M; Samuel, C E; Mak, T W; Hovanessian, A G; Jeang, K T; Williams, B R.
Afiliación
  • McMillan NA; Department of Cancer Biology, Cleveland Clinic Foundation, Ohio 44195, USA.
Virology ; 213(2): 413-24, 1995 Nov 10.
Article en En | MEDLINE | ID: mdl-7491766
ABSTRACT
We present evidence that the HIV-1 Tat protein and the RNA-dependent cellular protein kinase, PKR, interact with each other both in vitro and in vivo. Using GST fusion chromatography, we demonstrate that PKR, interacts directly with the HIV-1 Tat protein. The region in Tat sufficient for binding PKR maps within amino acids 20 to 72. In in vitro assays, the two-exon form of Tat (Tat 86) was phosphorylated by PKR, while the one exon form of Tat (Tat 72) inhibited PKR autophosphorylation and substrate phosphorylation. The ability of Tat to interact with PKR was demonstrated in both yeast and mammalian cells. Expression of PKR in yeast results in a growth suppressor phenotype which was reversed by coexpression of a one exon form of Tat. Expression of Tat 72 in HeLa cells resulted in direct interaction with PKR as detected by coimmunprecipitation with a Tat antibody. Tat and PKR also form a coimmunoprecipitable complex in cell-free extracts prepared from productively infected T lymphocytes. The interaction of Tat with PKR provides a potential mechanism by which HIV could suppress the interferon system.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Productos del Gen tat / VIH-1 / Proteínas Serina-Treonina Quinasas Límite: Humans Idioma: En Revista: Virology Año: 1995 Tipo del documento: Article País de afiliación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Productos del Gen tat / VIH-1 / Proteínas Serina-Treonina Quinasas Límite: Humans Idioma: En Revista: Virology Año: 1995 Tipo del documento: Article País de afiliación: Estados Unidos
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