SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription.

The transcription factor NF-kappaB plays important roles in inflammation and cell survival. In this study, we identified SINK, an NF-kappaB-inducible protein. Overexpression of SINK inhibited NF-kappaB-dependent transcription induced by tumor necrosis factor (TNF) stimulation or its downstream signaling proteins but did not inhibit NF-kappaB translocation to the nucleus and binding ...
to DNA. Co-immunoprecipitation and in vitro kinase assays indicated that SINK specifically interacted with the NF-kappaB transactivator p65 and inhibited p65 phosphorylation by the catalytic subunit of protein kinase A, which has previously been shown to regulate NF-kappaB activation. Consistent with its role in inhibition of NF-kappaB-dependent transcription, SINK also sensitized cells to apoptosis induced by TNF and TRAIL (TNF-related apoptosis-inducing ligand). Taken together, these data suggest that SINK is critically involved in a novel negative feedback control pathway of NF-kappaB-induced gene expression.
Mesh Terms:
Active Transport, Cell Nucleus, Amino Acid Sequence, Apoptosis, Cell Cycle Proteins, Cell Line, Cloning, Molecular, Feedback, Gene Expression, Humans, Molecular Sequence Data, NF-kappa B, Protein-Serine-Threonine Kinases, Repressor Proteins, Sequence Homology, Amino Acid, Transcription Factor RelA, Transcription Factors, Transcription, Genetic, Two-Hybrid System Techniques
J. Biol. Chem.
Date: Jul. 18, 2003
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