Regulation of folliculin (the BHD

详细信息    查看全文

• 作者：Xianghua Piao ; Toshiyuki Kobayashi ; Lu Wang ; Masatoshi Shiono ; Yumiko Takagi ; Guodong Sun ; Masaaki Abe ; Yoshiaki Hagiwara ; Danqing Zhang ; Kazuo Okimoto ; Mami Kouchi ; Izumi Matsumoto ; Okio Hino
• 关键词：FLCN ; Tsc2 ; BHD ; mTOR ; AMPK ; S6K ; Phosphorylation ; Rheb
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2009
• 出版时间：6 November 2009
• 年：2009
• 卷：389
• 期：1
• 页码：16-21
• 全文大小：622 K

文摘

The Birt–Hogg–Dubé gene (BHD) encodes the tumor suppressor protein folliculin (FLCN). The function of FLCN has recently been implicated in the regulation of rapamycin-sensitive mTOR complex (mTORC1). Reciprocally, the mTORC1-dependent phosphorylation of FLCN was reported. However, precise mechanism of FLCN phosphorylation and functional interaction of FLCN with tuberin, the product of tuberous sclerosis 2 gene (TSC2) which is a negative regulator of mTORC1, are unclear. Here we report that multiple phosphorylation in FLCN are evoked by downregulation of tuberin as well as by Rheb expression. We found that phosphorylation at Ser62 and Ser302 are differently regulated by mTORC1-dependent pathway. Some unknown kinases downstream of tuberin-mTORC1 are thought to directly phosphorylate FLCN. Interestingly, our results also suggest that the complex formation of FLCN with AMPK is modulated by FLCN phosphorylation. These results suggest that FLCN is involved in a novel mechanism of signal transduction downstream of tuberin.