Interaction of folliculin (Birt-Hogg-Dubé gene product) with a novel Fnip1-like (FnipL/Fnip2) protein

Y. Takagi, T. Kobayashi, M. Shiono, L. Wang, X. Piao, G. Sun, D. Zhang, M. Abe, Y. Hagiwara, K. Takahashi, O. Hino

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    95 Citations (Scopus)

    Abstract

    Birt-Hogg-Dubé (BHD) syndrome is characterized by the development of pneumothorax, hair folliculomas and renal tumors and the responsible BHD gene is thought to be a tumor suppressor. The function of folliculin (Flcn), encoded by BHD, is totally unknown, although its interaction with Fnip1 has been reported. In this study, we identified a novel protein binding to Flcn, which is highly homologous to Fnip1, and which we named FnipL (recently reported in an independent study as Fnip2). The interaction between FnipL/Fnip2 and Flcn may be mediated mainly by the C-terminal domains of each protein as is the case for the Flcn-Fnip1 interaction. FnipL/Fnip2 and Flcn were located together in the cytoplasm in a reticular pattern, although solely expressed Flcn was found mainly in the nucleus. Cytoplasmic retention of Flcn was canceled with C-terminal truncation of FnipL/Fnip2, suggesting that FnipL/Fnip2 regulates Flcn distribution through their complex formation. By the employment of siRNA, we observed a decrease in S6K1 phosphorylation in the BHD-suppressed cell. We also observed a decrease in S6K1 phosphorylation in FNIP1- and, to a lesser extent, in FNIPL/FNIP2-suppressed cells. These results suggest that Flcn-FnipL/Fnip2 and Flcn-Fnip1 complexes positively regulate S6K1 phosphorylation and that FnipL/Fnip2 provides an important clue to elucidating the function of Flcn and the pathogenesis of BHD.

    Original languageEnglish
    Pages (from-to)5339-5347
    Number of pages9
    JournalOncogene
    Volume27
    Issue number40
    DOIs
    Publication statusPublished - 2008 Sep 11

    Keywords

    • AMPK
    • BHD
    • Fnip1
    • FnipL/Fnip2
    • S6K1

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics
    • Cancer Research

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  • Cite this

    Takagi, Y., Kobayashi, T., Shiono, M., Wang, L., Piao, X., Sun, G., Zhang, D., Abe, M., Hagiwara, Y., Takahashi, K., & Hino, O. (2008). Interaction of folliculin (Birt-Hogg-Dubé gene product) with a novel Fnip1-like (FnipL/Fnip2) protein. Oncogene, 27(40), 5339-5347. https://doi.org/10.1038/onc.2008.261