Abstract
SINK is a p65-interacting protein that inhibits PKAc-induced phosphorylation of p65 and NF-kappaB transcriptional competence. We identified a SINK-homologous serine/threonine kinase SHIK. SHIK is ubiquitously expressed and is localized in the cytoplasm. Overexpression of SHIK inhibits TNF-triggered NF-kappaB activation in reporter gene assays. Overexpression of SHIK also inhibits p53-mediated transcription in reporter gene assays, while a point mutant (D197-->I) of SHIK potentiates p53-mediated transcription. Our findings suggest that SHIK is a negative regulator of NF-kappaB- and p53-mediated gene transcription.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Cell Cycle Proteins
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Cell Line
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Cloning, Molecular
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Humans
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Molecular Sequence Data
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NF-kappa B / metabolism*
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Phosphorylation
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Precipitin Tests
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Protein Serine-Threonine Kinases
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Repressor Proteins
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Sequence Homology, Amino Acid
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Transcription, Genetic / physiology*
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Tumor Necrosis Factor-alpha / physiology*
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Tumor Suppressor Protein p53 / physiology*
Substances
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Cell Cycle Proteins
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NF-kappa B
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Recombinant Proteins
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Repressor Proteins
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TRIB3 protein, human
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Transcription Factors
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Tumor Necrosis Factor-alpha
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Tumor Suppressor Protein p53
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Protein Serine-Threonine Kinases