期刊
OPEN BIOLOGY
卷 2, 期 -, 页码 -出版社
ROYAL SOC
DOI: 10.1098/rsob.120071
关键词
Birt - Hogg - Dube syndrome; folliculin; renal cell carcinoma; DENN
资金
- Myrovlytis Trust
- Bill and Melinda Gates Foundation
- BBSRC studentship
- Wellcome Trust
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.
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