Modulation of NFAT-dependent gene expression by the RhoA signaling pathway in T cells

被引:17
|
作者
Helms, Whitney S.
Jeffrey, Jerry L.
Holmes, Derek A.
Townsend, Michael B.
Clipstone, Neil A.
Su, Lishan
机构
[1] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA
[2] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
[3] Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA
[4] Loyola Univ, Sch Med, Dept Pharmacol, Maywood, IL 60153 USA
[5] Ctr Dis Control & Prevent, Atlanta, GA 30329 USA
[6] Univ N Carolina, Dept Microbiol & Immunol, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA
关键词
GTPase; HIV-1; IL-2;
D O I
10.1189/jlb.0206120
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We have reported previously that p115Rho guanine nucleotide exchange factor, its upstream activator G alpha 13, 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 IL-2 promoter during T cell activation.
引用
收藏
页码:361 / 369
页数:9
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