Ciliary localization of folliculin mediated via a kinesin-2-binding motif is required for its functions in mTOR regulation and tumor suppression
| Autor: | Bo Ai, Guangsen Bao, Yazhe Ren, Yunlong Zhang, Yu Dai, Yu Jiang, Ying Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cell signaling
Biophysics Kinesins mTORC1 Biochemistry mTORC2 Article 03 medical and health sciences Structural Biology Intraflagellar transport Proto-Oncogene Proteins Genetics Humans Point Mutation Genes Tumor Suppressor Amino Acid Sequence Cilia Folliculin Molecular Biology PI3K/AKT/mTOR pathway 030304 developmental biology 0303 health sciences Chemistry Cilium TOR Serine-Threonine Kinases Tumor Suppressor Proteins 030302 biochemistry & molecular biology Cell Biology Cell biology HEK293 Cells Kinesin Protein Binding |
| Zdroj: | FEBS Lett |
| Popis: | Folliculin (FLCN) is a tumor suppressor protein involved in many cellular processes, including cell signaling, apoptosis, and autophagy. In ciliated cells, FLCN localizes to primary cilia and controls mTORC1 signaling in response to flow stress. Here, we show that the ciliary localization of FLCN requires its interaction with kinesin-2, the motor protein for anterograde intraflagellar transport. FLCN binds to kinesin-2 through a loop region in the middle of the protein. Single point mutations within this region of FLCN disrupt its kinesin-2 binding and ciliary entry. The mutants lose the ability to suppress the abnormal mTORC1/2 signaling activities and anchorage-independent growth of FLCN-deficient tumor cells. These observations suggest that ciliary localization of FLCN is essential for its function as a tumor suppressor. |
| Databáze: | OpenAIRE |
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