Imperial College London

ProfessorDavidCarling

Faculty of MedicineInstitute of Clinical Sciences

Professor of Biochemistry
 
 
 
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Contact

 

+44 (0)20 3313 4313david.carling

 
 
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Location

 

3rd Fl CRBHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Siggs:2016:10.1073/pnas.1607592113,
author = {Siggs, OM and Stockenhuber, A and Deobagkar-Lele, M and Bull, KR and Crockford, TL and Kingston, BL and Crawford, G and Anzilotti, C and Steeples, V and Ghaffari, S and Czibik, G and Bellahcene, M and Watkins, H and Ashrafian, H and Davies, B and Woods, A and Carling, D and Yavari, A and Beutler, B and Cornall, RJ},
doi = {10.1073/pnas.1607592113},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
pages = {E3706--E3715},
title = {Mutation of Fnip1 is associated with B-cell deficiency, cardiomyopathy, and elevated AMPK activity},
url = {http://dx.doi.org/10.1073/pnas.1607592113},
volume = {113},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Folliculin (FLCN) is a tumor-suppressor protein mutated in the Birt–Hogg–Dubé (BHD) syndrome, which associates with two paralogous proteins, folliculin-interacting protein (FNIP)1 and FNIP2, forming a complex that interacts with the AMP-activated protein kinase (AMPK). Although it is clear that this complex influences AMPK and other metabolic regulators, reports of its effects have been inconsistent. To address this issue, we created a recessive loss-of-function variant of Fnip1. Homozygous FNIP1 deficiency resulted in profound B-cell deficiency, partially restored by overexpression of the antiapoptotic protein BCL2, whereas heterozygous deficiency caused a loss of marginal zone B cells. FNIP1-deficient mice developed cardiomyopathy characterized by left ventricular hypertrophy and glycogen accumulation, with close parallels to mice and humans bearing gain-of-function mutations in the γ2 subunit of AMPK. Concordantly, γ2-specific AMPK activity was elevated in neonatal FNIP1-deficient myocardium, whereas AMPK-dependent unc-51–like autophagy activating kinase 1 (ULK1) phosphorylation and autophagy were increased in FNIP1-deficient B-cell progenitors. These data support a role for FNIP1 as a negative regulator of AMPK.
AU - Siggs,OM
AU - Stockenhuber,A
AU - Deobagkar-Lele,M
AU - Bull,KR
AU - Crockford,TL
AU - Kingston,BL
AU - Crawford,G
AU - Anzilotti,C
AU - Steeples,V
AU - Ghaffari,S
AU - Czibik,G
AU - Bellahcene,M
AU - Watkins,H
AU - Ashrafian,H
AU - Davies,B
AU - Woods,A
AU - Carling,D
AU - Yavari,A
AU - Beutler,B
AU - Cornall,RJ
DO - 10.1073/pnas.1607592113
EP - 3715
PY - 2016///
SN - 1091-6490
SP - 3706
TI - Mutation of Fnip1 is associated with B-cell deficiency, cardiomyopathy, and elevated AMPK activity
T2 - Proceedings of the National Academy of Sciences of the United States of America
UR - http://dx.doi.org/10.1073/pnas.1607592113
UR - http://hdl.handle.net/10044/1/39189
VL - 113
ER -