cis-Acting Element-specific Transcriptional Activity of Differentially Phosphorylated Nuclear Factor-κB
作者： Josef Anrather , Gianfranco Racchumi , Costantino Iadecola
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摘要: Phosphorylation of nuclear factor-κB (NF-κB) subunits emerges as a mechanism by which transcriptional activity NF-κB complexes is regulated in an inhibitor κB-independent fashion. As the main transactivator, p65 subunit has outstanding position hierarchy proteins. multiply phosphorylated protein with phosphorylation sites C-terminal transactivation domain and N-terminal Rel homology (RHD). In this study, we describe two previously non-reported phospho-acceptor within RHD. We show that differential serine residues RHD modulates cis-acting element promoter-specific context, thus leading to state-dependent gene expression profile. RelA-/- mouse embryonic fibroblasts reconstituted wild-type or phosphorylation-deficient mutants showed distinctive profile synthetic κB-dependent reporters well endogenous genes. Hypophosphorylated did not display element-specific changes DNA binding dimerization behavior. This study shows for first time site-specific can target transcription factor particular subset
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