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Mutations in the renal tumour suppressor protein, folliculin, lead to proliferative skin lesions, lung complications and renal cell carcinoma. Folliculin has been reported to interact with AMP-activated kinase, a key component of the mammalian target of rapamycin pathway. Most cancer-causing mutations lead to a carboxy-terminal truncation of folliculin, pointing to a functional importance of this domain in tumour suppression. We present here the crystal structure of folliculin carboxy-terminal domain and demonstrate that it is distantly related to differentially expressed in normal cells and neoplasia (DENN) domain proteins, a family of Rab guanine nucleotide exchange factors (GEFs). Using biochemical analysis, we show that folliculin has GEF activity, indicating that folliculin is probably a distantly related member of this class of Rab GEFs.

Original publication




Journal article


Open Biol

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Birt–Hogg–Dubé syndrome, DENN, folliculin, renal cell carcinoma, Amino Acid Sequence, Carcinoma, Renal Cell, Crystallography, X-Ray, Death Domain Receptor Signaling Adaptor Proteins, Electrophoresis, Polyacrylamide Gel, Guanine Nucleotide Exchange Factors, Guanosine Diphosphate, Guanosine Triphosphate, Humans, Kidney Neoplasms, Models, Molecular, Molecular Sequence Data, Mutation, Protein Structure, Secondary, Protein Structure, Tertiary, Proto-Oncogene Proteins, Sequence Homology, Amino Acid, Tumor Suppressor Proteins