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The Hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to mTORC1
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The Hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to mTORC1
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Journal Article
The Hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to mTORC1
2015
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Adaptor Proteins, Signal Transducing - genetics
/ Adaptor Proteins, Signal Transducing - metabolism
/ Biomedical and Life Sciences
/ Humans
/ Intracellular Signaling Peptides and Proteins - genetics
/ Intracellular Signaling Peptides and Proteins - metabolism
/ Mechanistic Target of Rapamycin Complex 1
/ Multiprotein Complexes - metabolism
/ Original
/ Phosphoproteins - metabolism
/ Protein-Serine-Threonine Kinases - metabolism
