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

J Biol Chem. 2003 Jul 18;278(29):27072-9. doi: 10.1074/jbc.M209814200. Epub 2003 May 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acid Sequence
  • Apoptosis
  • Cell Cycle Proteins
  • Cell Line
  • Cloning, Molecular
  • Feedback
  • Gene Expression
  • Humans
  • In Vitro Techniques
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • Protein Serine-Threonine Kinases
  • Repressor Proteins
  • Sequence Homology, Amino Acid
  • Transcription Factor RelA
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Two-Hybrid System Techniques


  • Cell Cycle Proteins
  • NF-kappa B
  • Repressor Proteins
  • TRIB3 protein, human
  • Transcription Factor RelA
  • Transcription Factors
  • Protein Serine-Threonine Kinases