SINK Is a p65-interacting Negative Regulator of NF-κB-dependent Transcription*

By Min Wu, Liang-Guo Xu, Z. Zhai, H. Shu. Journal of Biological Chemistry, 2003

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The transcription factor NF-κB plays important roles in inflammation and cell survival. In this study, we identified SINK, an NF-κB-inducible protein. Overexpression of SINK inhibited NF-κB-dependent transcription induced by tumor necrosis factor (TNF) stimulation or its downstream signaling proteins but did not inhibit NF-κB translocation to the nucleus and binding to DNA. Co-immunoprecipitation and in vitro kinase assays indicated that SINK specifically interacted with the NF-κB transactivator p65 and inhibited p65 phosphorylation by the catalytic subunit of protein kinase A, which has previously been shown to regulate NF-κB activation. Consistent with its role in inhibition of NF-κB-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-κB-induced gene expression.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/b8ec2c4fe8846116685dadb1bbb275c28f959c9e