Siggs OM., Stockenhuber A., Deobagkar-Lele M., Bull KR., Crockford TL., Kingston BL., Crawford G., Anzilotti C., Steeples V., Ghaffari S., Czibik G., Bellahcene M., Watkins H., Ashrafian H., Davies B., Woods A., Carling D., Yavari A., Beutler B., Cornall RJ.

Significance 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.

Mutation of Fnip1 is associated with B-cell deficiency, cardiomyopathy, and elevated AMPK activity

Siggs OM., Stockenhuber A., Deobagkar-Lele M., Bull KR., Crockford TL., Kingston BL., Crawford G., Anzilotti C., Steeples V., Ghaffari S., Czibik G., Bellahcene M., Watkins H., Ashrafian H., Davies B., Woods A., Carling D., Yavari A., Beutler B., Cornall RJ.

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