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Ciliary localization of folliculin mediated via a kinesin‐2‐binding motif is required for its functions in mTOR regulation and tumor suppression
Author(s) -
Zhang Yunlong,
Liu Ying,
Dai Yu,
Ren Yazhe,
Bao Guangsen,
Ai Bo,
Jiang Yu
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13959
Subject(s) - folliculin , cilium , microbiology and biotechnology , biology , kinesin , suppressor , ciliogenesis , signal transducing adaptor protein , signal transduction , chemistry , microtubule , genetics , cancer , gene
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.