Identification of a novel serine/threonine kinase that inhibits TNF-induced NF-kappaB activation and p53-induced transcription.
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.
D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D002460:Cell Line; D003001:Cloning, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D018797:Cell Cycle Proteins; D016328:NF-kappa B; D011994:Recombinant Proteins; D012097:Repressor Proteins; C474831:TRIB3 protein, human; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D017346:Protein Serine-Threonine Kinases