| Citation | Gharbi H, Fabretti F, Bharill P, Rinschen M, Brinkkotter S, Frommolt P, Burst V, Schermer B, Benzing T, Muller RU. Loss of the Birt-Hogg-Dube gene product folliculin induces longevity in a hypoxia-inducible factor-dependent manner. Aging Cell, 2013. |
| PubMed ID | 23566034 |
| Short Description | Loss of the Birt-Hogg-Dube gene product folliculin induces longevity in a hypoxia-inducible factor-dependent manner. GEO Record: GSE43207 Platform: GPL11346 Download gene-centric, log2 transformed data: WBPaper00042236.ce.mr.csv |
| # of Conditions | 6 |
Full Description
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Signaling through the hypoxia-inducible factor hif-1 controls longevity, metabolism, and stress resistance in Caenorhabditis elegans. Hypoxia-inducible factor (HIF) protein levels are regulated through an evolutionarily conserved ubiquitin ligase complex. Mutations in the VHL gene, encoding a core component of this complex, cause a multitumor syndrome and renal cell carcinoma in humans. In the nematode, deficiency in vhl-1 promotes longevity mediated through HIF-1 stabilization. However, this longevity assurance pathway is not yet understood. Here, we identify folliculin (FLCN) as a novel interactor of the hif-1/vhl-1 longevity pathway. FLCN mutations cause Birt-Hogg-Dube syndrome in humans, another tumor syndrome with renal tumorigenesis reminiscent of the VHL disease. Loss of the C. elegans ortholog of FLCN F22D3.2 significantly increased lifespan and enhanced stress resistance in a hif-1-dependent manner. F22D3.2, vhl-1, and hif-1 control longevity by a mechanism distinct from insulin-like signaling. Daf-16 deficiency did not abrogate the increase in lifespan mediated by flcn-1. These findings define FLCN as a player in HIF-dependent longevity signaling and connect organismal aging, stress resistance, and regulation of longevity with the formation of renal cell carcinoma. Experimental Details: WBPaper00042236:N2_rep1 WBPaper00042236:flcn-1(ok975)_rep1 WBPaper00042236:flcn-1(ok975)_rep2 WBPaper00042236:flcn-1(ok975)_rep3 WBPaper00042236:N2_rep2 WBPaper00042236:N2_rep3. |
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