PMID:10400814

Citation	Demarchi, F, Gutierrez, MI and Giacca, M (1999) Human immunodeficiency virus type 1 tat protein activates transcription factor NF-kappaB through the cellular interferon-inducible, double-stranded RNA-dependent protein kinase, PKR. J. Virol. 73:7080-6
Abstract	The transactivator protein of human immunodeficiency virus type 1 (HIV-1) (Tat) is a powerful activator of nuclear factor-kappaB (NF-kappaB), acting through degradation of the inhibitor IkappaB-alpha (F. Demarchi, F. d'Adda di Fagagna, A. Falaschi, and M. Giacca, J. Virol. 70:4427-4437, 1996). Here, we show that this activity of Tat requires the function of the cellular interferon-inducible protein kinase PKR. Tat-mediated NF-kappaB activation and transcriptional induction of the HIV-1 long terminal repeat were impaired in murine cells in which the PKR gene was knocked out. Both functions were restored by cotransfection of Tat with the cDNA for PKR. Expression of a dominant-negative mutant of PKR specifically reduced the levels of Tat transactivation in different human cell types. Activation of NF-kappaB by Tat required integrity of the basic domain of Tat; previous studies have indicated that this domain is necessary for specific Tat-PKR interaction.
Links	PubMed PMC112801
Keywords	3T3 Cells; Animals; Gene Products, tat/genetics; Gene Products, tat/metabolism; HIV-1/metabolism; Humans; Interferons; Mice; Mutagenesis; NF-kappa B/metabolism; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; eIF-2 Kinase/metabolism; tat Gene Products, Human Immunodeficiency Virus
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HV1BR:TAT		GO:0051092: positive regulation of NF-kappaB transcription factor activity	ECO:0000314:		P		Figure 3B shows the gel retardation analysis of NF-kappaB complexes induced by Tat in both NIH 3T3 and PKR knockout mouse cells. The analysis reveals that neither the tat protein nor the PKR (a Cellular Interferon-Inducible, Double-Stranded RNA-Dependent Protein Kinase) can activate the NF-kappa-B transcription factor (lanes 1 and 2). When the tat protein and PKR worked together (Lane 3), this produced a positive activation of NF-kappaB. This proves that the tat protein must activate NF-kappaB through PKR.	complete CACAO 6522
HV1BR:TAT	involved_in	GO:0051092: positive regulation of NF-kappaB transcription factor activity	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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