Volume 25, No 12, Dec 2015
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 25 Issue 12, December 2015: 1299-1313
ORIGINAL ARTICLES
The Hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to mTORC1
Carsten Gram Hansen1, Yuen Lam Dora Ng1, Wai-Ling Macrina Lam1, Steven W Plouffe1 and Kun-Liang Guan1
1Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA
Correspondence: Kun-Liang Guan, Tel: +1 8588227945(kuguan@ucsd.edu)
YAP and TAZ are transcriptional co-activators and function as the major effectors of the Hippo tumor suppressor pathway, which controls cell growth, tissue homeostasis, and organ size. Here we show that YAP/TAZ play an essential role in amino acid-induced mTORC1 activation, particularly under nutrient-limiting conditions. Mechanistically, YAP/TAZ act via the TEAD transcription factors to induce expression of the high-affinity leucine transporter LAT1, which is a heterodimeric complex of SLC7A5 and SLC3A2. Deletion of YAP/TAZ abolishes expression of LAT1 and reduces leucine uptake. Re-expression of SLC7A5 in YAP/TAZ knockout cells restores leucine uptake and mTORC1 activation. Moreover, SLC7A5 knockout cells phenocopies YAP/TAZ knockout cells which exhibit defective mTORC1 activation in response to amino acids. We further demonstrate that YAP/TAZ act through SLC7A5 to provide cells with a competitive growth advantage. Our study provides molecular insight into the mechanism of YAP/TAZ target genes in cell growth regulation.
doi:10.1038/cr.2015.140
FULL TEXT | PDF
Browse 2645
