Interaction of folliculin (Birt-Hogg-Dubé gene product) with a novel Fnip1-like (FnipL/Fnip2) protein
| Autor: | Kazuhisa Takahashi, Toshiyuki Kobayashi, Danqing Zhang, Okio Hino, Yoshiaki Hagiwara, Guodong Sun, Xianghua Piao, Masatoshi Shiono, Masaaki Abe, Yumiko Takagi, Lu Wang |
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| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Cytoplasm Cell Blotting Western P70-S6 Kinase 1 Biology Kidney Transfection Polymerase Chain Reaction law.invention Gene product law Proto-Oncogene Proteins Chlorocebus aethiops Genetics medicine Animals Humans Immunoprecipitation RNA Messenger Folliculin Phosphorylation RNA Small Interfering Molecular Biology Gene Carcinoma Renal Cell Cells Cultured Ribosomal Protein S6 Kinases Tumor Suppressor Proteins Syndrome Blotting Northern Molecular biology Kidney Neoplasms Cell biology medicine.anatomical_structure Protein Biosynthesis COS Cells Suppressor Carrier Proteins HeLa Cells Protein Binding |
| Zdroj: | Oncogene. 27(40) |
| ISSN: | 1476-5594 |
| Popis: | Birt-Hogg-Dube (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. |
| Databáze: | OpenAIRE |
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