Folliculin
Folliculin also known as FLCN, BHD, FLCL, FLCN_HUMAN, MGC17998, or MGC23445 is a protein associated with Birt-Hogg-Dubé syndrome. It is encoded by the Folliculin gene sometimes also referred to as the BHD gene.
The function of the folliculin protein has yet to be determined but current research suggests it may act as a tumor suppressor. Tumor suppressors help control the growth and division of cells.[1]
Gene
Structure
The FLCN gene consists of 14 exons.[2]
Location
Cytogenetic Location: The FLCN gene is located on the short (p) arm of chromosome 17 at position 11.2. (17p11.2).[1]
Molecular Location on chromosome 17: base pairs 17,056,250 to 17,081,220
Function
Using coimmunoprecipitation of FNIP1 and FLCN expressed in HEK293 cells and in vitro binding assays, the C-terminus of FLCN and amino acids 300 to 1166 of FNIP1 were shown to be required for optimal FLCN-FNIP1 binding.[3] FLCN and FNIP1 colocalized to the cytoplasm in a reticular pattern. FNIP1 was phosphorylated by AMPK and its phosphorylation was inhibited in a dose-dependent manner by an AMPK inhibitor, resulting in reduced FNIP1 expression. FLCN phosphorylation was diminished by rapamycin and amino acid starvation and facilitated by FNIP1 overexpression, suggesting that FLCN phosphorylation may be regulated by mTOR and AMPK signaling. FLCN and FNIP1 may be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways.[3]
A novel signaling pathway consolidating recent research on the Folliculin protein has been devised at BHDSyndrome.org. This is meant to act as an aid to researchers in the field and can be found here.
References
- ↑ 1.0 1.1 "Folliculin". Genetics Home Reference.
- ↑ Nickerson ML, Warren MB, Toro JR, Matrosova V, Glenn G, Turner ML, Duray P, Merino M, Choyke P, Pavlovich CP, Sharma N, Walther M, Munroe D, Hill R, Maher E, Greenberg C, Lerman MI, Linehan WM, Zbar B, Schmidt LS (August 2002). "Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome". Cancer Cell 2 (2): 157–64. doi:10.1016/S1535-6108(02)00104-6. PMID 12204536.
- ↑ 3.0 3.1 Baba M, Hong SB, Sharma N, Warren MB, Nickerson ML, Iwamatsu A, Esposito D, Gillette WK, Hopkins RF, Hartley JL, Furihata M, Oishi S, Zhen W, Burke TR, Linehan WM, Schmidt LS, Zbar B (October 2006). "Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling". Proc. Natl. Acad. Sci. U.S.A. 103 (42): 15552–7. doi:10.1073/pnas.0603781103. PMC 1592464. PMID 17028174.
External links
- FLCN protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
- Baba, M. et al. "Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling."
- The BHD Foundation supports research into BHD syndrome and maintains the world's first website dedicated to BHD syndrome - BHDSyndrome.org
- Human Folliculin variants, listing maintained by the European Birt-Hogg-Dube Consortium.