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The Hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to mTORC1
Open accessAbstract
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.
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“Notably, the expression of its partner protein solute carrier family 3 member 2 (SLC3A2), which forms a heterodimer with SLC7A5 to facilitate leucine transport and mTORC1 activation (49), remained unaffected (Figure 6B).”
From YAP/TAZ mediates resistance to KRAS inhibitors through inhibiting proapoptosis and activating the SLC7A5/mTOR axis (2024) · cites this paper as [49]
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“YAP/TAZ also increase the expression of genes that encode the leucine transporter LAT1 (52)”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [52]
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Metadata
- Authors
- Hansen, C. G., Ng, Y. L. D., Lam, W.-L. M., Plouffe, S. W., & Guan, K.-L.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Guan, Kun-Liang
- Venue
- Cell Research
- Published
- 2015-11-27
- Volume
- 25
- Issue
- 12
- Pages
- 1299-1313
- ISSN
- 1001-0602 (ISSN-L)
- 1748-7838
- PMC
- PMC4670996
- OpenAlex
- W2180757710
- Cited by
- 212
- References
- 60
- Citations by year
- 2026: 15 · 2025: 24 · 2024: 25 · 2023: 19 · 2022: 17 · 2021: 22 · 2020: 26 · 2019: 18 · 2018: 21 · 2017: 17 · 2016: 8
- FWCI
- 8.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Danmarks Frie Forskningsfond
- National Institutes of Health (CA132809)
- University of California, San Diego (T32 GM007752)
- National Eye Institute (R01EY022611, EY0226116)
- National Cancer Institute (R35CA196878, CA132809, R01CA108941, R01CA132809)
- National Institute of General Medical Sciences (T32GM007752)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- Hippo signaling pathway, YAP, TAZ, mTORC1, amino acid signaling, leucine uptake, LAT1, SLC7A5, SLC3A2, TEAD transcription factors, nutrient limitation, cell growth regulation, transcriptional coactivator
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Hippo Signaling Pathway, YAP-Signaling Proteins, Transcriptional Coactivator with PDZ-Binding Motif Proteins, Amino Acids, Cells, Cultured, Humans, Phosphoproteins, Transcription Factors, Signal Transduction, Trans-Activators, Protein Serine-Threonine Kinases, Multiprotein Complexes, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Cell Proliferation, HEK293 Cells, TOR Serine-Threonine Kinases
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