BHD; FLCL; BHD skin lesion fibrofolliculoma protein; Birt-Hogg-Dube syndrome protein
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. 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.
Organism species: Homo sapiens (Human)
Organism species: Mus musculus (Mouse)
Organism species: Rattus norvegicus (Rat)