Mutation of Fnip1 is associated with B-cell deficiency, cardiomyopathy, and elevated AMPK activity
Abstract
Cellular metabolism is tightly regulated by AMP-activated protein kinase (AMPK): the function of which is influenced by folliculin (FLCN), folliculin-interacting protein (FNIP)1, and FNIP2. FLCN is a known tumor-suppressor protein that is mutated in Birt-Hogg-Dubé syndrome, whereas FNIP1 and FNIP2 are binding partners of FLCN. Previous reports have suggested that the FLCN/FNIP1/FNIP2 complex acts a positive regulator of AMPK, whereas other reports suggest the opposite. Using a new mouse model of FNIP1 deficiency, our findings support the latter: we found that mutation of Fnip1 leads to B-cell deficiency and the development of a cardiomyopathy similar to mice and humans with gain-of-function mutations in AMPK.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- June 2016
- DOI:
- 10.1073/pnas.1607592113
- Bibcode:
- 2016PNAS..113E3706S