Abstract:
:The human tumor necrosis factor alpha (TNF-alpha) gene is rapidly activated in response to multiple signals of stress and inflammation. We have identified transcription factors present in the TNF-alpha enhancer complex in vivo following ionophore stimulation (ATF-2/Jun and NFAT) and virus infection (ATF-2/Jun, NFAT, and Sp1), demonstrating a novel role for NFAT and Sp1 in virus induction of gene expression. We show that virus infection results in calcium flux and calcineurin-dependent NFAT dephosphorylation; however, relatively lower levels of NFAT are present in the nucleus following virus infection as compared to ionophore stimulation. Strikingly, Sp1 functionally synergizes with NFAT and ATF-2/c-jun in the activation of TNF-alpha gene transcription and selectively associates with the TNF-alpha promoter upon virus infection but not upon ionophore stimulation in vivo. We conclude that the specificity of TNF-alpha transcriptional activation is achieved through the assembly of stimulus-specific enhancer complexes and through synergistic interactions among the distinct activators within these enhancer complexes.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Falvo JV,Uglialoro AM,Brinkman BM,Merika M,Parekh BS,Tsai EY,King HC,Morielli AD,Peralta EG,Maniatis T,Thanos D,Goldfeld AEdoi
10.1128/mcb.20.6.2239-2247.2000subject
Has Abstractpub_date
2000-03-01 00:00:00pages
2239-47issue
6eissn
0270-7306issn
1098-5549journal_volume
20pub_type
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