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Open Biol. 2012 Aug;2(8):120071. doi: 10.1098/rsob.120071.

Crystal structure of folliculin reveals a hidDENN function in genetically inherited renal cancer.

Author information

1
Department of Biochemistry , University of Cambridge, Sanger Building, 80 Tennis Court Road, Cambridge CB2 1GA, UK. rn229@cam.ac.uk

Abstract

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.

KEYWORDS:

Birt–Hogg–Dubé syndrome; DENN; folliculin; renal cell carcinoma

PMID:
22977732
PMCID:
PMC3438538
DOI:
10.1098/rsob.120071
[Indexed for MEDLINE]
Free PMC Article

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