title: Modulation of NFAT-dependent gene expression by the RhoA signaling pathway in T cells.
abstract: We have reported previously that p115Rho guanine nucleotide exchange factor, its upstream activator Galpha13, and its effector RhoA are able to inhibit HIV-1 replication. Here, we show that RhoA is able to inhibit HIV-1 gene expression through the NFAT-binding site in the HIV long-terminal repeat. Constitutively active NFAT counteracts the inhibitory activity of RhoA, and inhibition of NFAT activation also inhibits HIV-1 gene expression. We have shown further that RhoA inhibits NFAT-dependent transcription and IL-2 production in human T cells. RhoA does not inhibit nuclear localization of NFAT but rather, inhibits its transcriptional activity. In addition, RhoA decreases the level of acetylated histone H3, but not NFAT occupancy, at the IL-2 promoter. These data suggest that activation of RhoA can modulate IL-2 gene expression by inhibiting the transcriptional activity of NFAT and chromatin structure at the IL-2 promoter during T cell activation.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA.
authors.forename: Whitney S
authors.initials: WS
authors.lastname: Helms
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Jeffrey
authors.forename: Derek A
authors.initials: DA
authors.lastname: Holmes
authors.forename: Michael B
authors.initials: MB
authors.lastname: Townsend
authors.forename: Neil A
authors.initials: NA
authors.lastname: Clipstone
authors.forename: Lishan
authors.initials: L
authors.lastname: Su
mesh_terms: D005786:Gene Expression Regulation; D017930:Genes, Reporter; D016325:HIV Long Terminal Repeat / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D008156:Luciferases / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D014161:Transduction, Genetic; D020742:rhoA GTP-Binding Protein / Q000502:physiology*
chemical_list: D050778:NFATC Transcription Factors; D008156:Luciferases; D020742:rhoA GTP-Binding Protein