Physical and functional interactions between STAT3 and KAP1

R. Tsuruma, N. Ohbayashi, S. Kamitani, O. Ikeda, N. Sato, R. Muromoto, Y. Sekine, K. Oritani, T. Matsuda

    Research output: Contribution to journalArticle

    46 Citations (Scopus)

    Abstract

    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 two-hybrid screening and identified KAP1/TIF1β as a novel STAT-binding partner. KAP1 is a universal corepressor protein for the Kruppel-associated box 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 interleukin (IL)-6-induced STAT3-dependent transcription and gene expression. Furthermore, reduction of KAP1 expression resulted in the marked 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.

    Original languageEnglish
    Pages (from-to)3054-3059
    Number of pages6
    JournalOncogene
    Volume27
    Issue number21
    DOIs
    Publication statusPublished - 2008 May 8

    Keywords

    • IL-6
    • KAP1
    • Phosphorylation
    • STAT3
    • Transcriptional regulation

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics
    • Cancer Research

    Fingerprint Dive into the research topics of 'Physical and functional interactions between STAT3 and KAP1'. Together they form a unique fingerprint.

  • Cite this

    Tsuruma, R., Ohbayashi, N., Kamitani, S., Ikeda, O., Sato, N., Muromoto, R., Sekine, Y., Oritani, K., & Matsuda, T. (2008). Physical and functional interactions between STAT3 and KAP1. Oncogene, 27(21), 3054-3059. https://doi.org/10.1038/sj.onc.1210952