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.