Journal article
Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth
AG Cox, A Tsomides, D Yimlamai, KL Hwang, J Miesfeld, GG Galli, BH Fowl, M Fort, KY Ma, MR Sullivan, AM Hosios, E Snay, M Yuan, KK Brown, EC Lien, S Chhangawala, ML Steinhauser, JM Asara, Y Houvras, B Link Show all
EMBO Journal | WILEY | Published : 2018
Abstract
The Hippo pathway and its nuclear effector Yap regulate organ size and cancer formation. While many modulators of Hippo activity have been identified, little is known about the Yap target genes that mediate these growth effects. Here, we show that yap−/− mutant zebrafish exhibit defects in hepatic progenitor potential and liver growth due to impaired glucose transport and nucleotide biosynthesis. Transcriptomic and metabolomic analyses reveal that Yap regulates expression of glucose transporter glut1, causing decreased glucose uptake and use for nucleotide biosynthesis in yap−/− mutants, and impaired glucose tolerance in adults. Nucleotide supplementation improves Yap deficiency phenotypes, ..
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Awarded by Damon Runyon Cancer Research Foundation
Funding Acknowledgements
This work was supported by an Irwin Arias Postdoctoral Fellowship (A.G.C.) and Liver Scholar Award (A.G.C.) from the American Liver Foundation, HDDC Pilot Feasibility Grant P30DK034854 (A.G.C.) and the NHMRC 1146558 (A.G.C.), NIH NIGMS T32GM007753 (K.L.H.), and by NIH NIDDK 1R01DK090311, 1R01DK105198, and R24OD017870 (W.G.). W.G. is a Pew Scholar in the Biomedical Sciences and supported by the Claudia Adams Barr Program for Innovative Cancer Research. M.G.V.H. acknowledges support as an HHMI faculty scholar and additional support from SU2C and the NIH. E.C.L. is a fellow supported by the Damon Runyon Cancer Research Foundation. J.M.A. is partially supported by NIH NCI grants 5P01CA120964 and 5P30CA006516. G.G.G. is supported by an American-Italian Cancer Foundation postdoctoral research fellowship.