Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth
Name
300053v1.full.pdf
Description
Submitted version
Size
3.58 MB
Format
Adobe PDF
Checksum (MD5)
859fa65e52c4c9038d7b11696788885b
Author(s)
Cox, Andrew G
Tsomides, Allison
Yimlamai, Dean
Hwang, Katie L
Miesfeld, Joel
Galli, Giorgio G
Fowl, Brendan H
Fort, Michael
Ma, Kimberly Y
Sullivan, Mark R
Date Issued
October 2018
Journal
EMBO Journal
Publisher
EMBO
Citation
Cox, Andrew G. et al. "Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth." EMBO Journal 37 (October 2018): e100294 © 2018 The Authors
Version
Original manuscript
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, indicating functional importance of glucose-fueled nucleotide biosynthesis. Yap-regulated glut1 expression and glucose uptake are conserved in mammals, suggesting that stimulation of anabolic glucose metabolism is an evolutionarily conserved mechanism by which the Hippo pathway controls organ growth. Together, our results reveal a central role for Hippo signaling in glucose metabolic homeostasis.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.15252/EMBJ.2018100294
