Folliculin, the Product of the Birt-Hogg-Dube Tumor Suppressor Gene, Interacts with the Adherens Junction Protein p0071 to Regulate Cell-Cell Adhesion
November 2012
in “
PloS one
”
TLDR The protein folliculin, involved in a rare disease, works with another protein to control how cells stick together and their organization, and changes in this interaction can lead to disease symptoms.
In the study of Birt-Hogg-Dube (BHD) syndrome, researchers identified a physical interaction between folliculin (FLCN), the protein encoded by the BHD gene, and p0071, a protein associated with cell-cell adhesion. They discovered that reducing FLCN levels increased cell-cell adhesion and disrupted cell polarity, effects that were also observed with reduced p0071 levels, suggesting that the FLCN-p0071 complex negatively regulates cell-cell adhesion. Additionally, FLCN was found to positively influence RhoA activity, which aligns with p0071's known function. In vivo experiments using mice with Flcn inactivation in their epidermis showed phenotypes such as delayed eyelid opening, wavy fur, hair loss, and epidermal hyperplasia, along with increased mTORC1 activity. These findings suggest that disruption of the FLCN-p0071 interaction can lead to changes in cell adhesion, cell polarity, and RhoA signaling, which may contribute to the development of diseases like emphysema and renal cell carcinoma.
