Stimulus-Specific Assembly of Enhancer Complexes on the Tumor Necrosis Factor Alpha Gene Promoter†

AUTOR(ES)

Falvo, James V.

FONTE

American Society for Microbiology

RESUMO

The human tumor necrosis factor alpha (TNF-α) gene is rapidly activated in response to multiple signals of stress and inflammation. We have identified transcription factors present in the TNF-α 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-α gene transcription and selectively associates with the TNF-α promoter upon virus infection but not upon ionophore stimulation in vivo. We conclude that the specificity of TNF-α transcriptional activation is achieved through the assembly of stimulus-specific enhancer complexes and through synergistic interactions among the distinct activators within these enhancer complexes.

Documentos Relacionados

• A stimulus-specific role for CREB-binding protein (CBP) in T cell receptor-activated tumor necrosis factor α gene expression
• The Chemistry of Olfactory Reception: Stimulus-Specific Protection from Sulfhydryl Reagent Inhibition
• Stimulus-specific neuronal oscillations in orientation columns of cat visual cortex.
• Stimulus-specific deactivation of chemotactic factor-induced cyclic AMP response and superoxide generation by human neutrophils.
• Stimulus-specific patterns of intracellular calcium levels in smooth muscle of ferret portal vein.