Physical and functional interactions between STAT3 and KAP1

概要

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Signal transducers and activators of transcription (STATs) mediate cell proliferation, differentiation, and survival in immune responses, hematopoiesis, neurogenesis, and other biological processes. For example, STAT3 has been reported to be constitutively activated in numerous cancer cells. To clarify the molecular mechanisms underlying the STAT activation, we performed yeast twohybrid screening and identified KAP1/TIF1β as a novel STAT-binding partner. KAP1 is a universal corepressor protein for the KRAB zinc finger protein superfamily of transcriptional repressors. We found endogenous KAP1 associated with endogenous STAT3 in vivo. Importantly, small-interfering RNA-mediated reduction of KAP1 expression enhanced IL-6-induced STAT3-dependent transcription and gene expression. Furthermore, reduction of KAP1 expression resulted in the marked nuclear accumulation of STAT3 phosphorylated on Ser727 in the nucleus, a modification that regulates its transcriptional activation. These results indicate that KAP1 may serve as a transcriptional regulator of the IL-6/STAT3 signaling pathway.
2008-05-08