The DOI matches its Crossref record; 48 of the 49 references it cites were found in a registry or an index.
Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathway
Open accessAbstract
TEA domain (TEAD) transcription factors bind to the coactivators YAP and TAZ and regulate the transcriptional output of the Hippo pathway, playing critical roles in organ size control and tumorigenesis. Protein S-palmitoylation attaches a fatty acid, palmitate, to cysteine residues and regulates protein trafficking, membrane localization and signaling activities. Using activity-based chemical probes, we discovered that human TEADs possess intrinsic palmitoylating enzyme-like activities and undergo autopalmitoylation at evolutionarily conserved cysteine residues under physiological conditions. We determined the crystal structures of lipid-bound TEADs and found that the lipid chain of palmitate inserts into a conserved deep hydrophobic pocket. Strikingly, palmitoylation did not alter TEAD's localization, but it was required for TEAD's binding to YAP and TAZ and was dispensable for its binding to the Vgll4 tumor suppressor. Moreover, palmitoylation-deficient TEAD mutants impaired TAZ-mediated muscle differentiation in vitro and tissue overgrowth mediated by the Drosophila YAP homolog Yorkie in vivo. Our study directly links autopalmitoylation to the transcriptional regulation of the Hippo pathway.
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“YAP/TAZ primarily pairs with the TEAD family of TFs to induce gene expression signatures that play an important role in cancer development, progression, and metastasis.435,436”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [436]
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Role of YAP/TAZ in mechanotransduction
Dupont, S., Morsut, L., Aragona, M., Enzo, E., Giulitti, S., Cordenonsi, M., Zanconato, F., Le Digabel, J., Forcato, M., Bicciato, S., et al. (2011) · Nature · doi:10.1038/nature10137 · Cited by 5,979
Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis
Menendez, J. A., & Lupu, R. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2222 · Cited by 2,941
TEAD mediates YAP-dependent gene induction and growth control
Zhao, B., Ye, X., Yu, J., Li, L., Li, W., Li, S., Yu, J., Lin, J. D., Wang, C.-Y., Chinnaiyan, A. M., et al. (2008) · Genes & Development · doi:10.1101/gad.1664408 · Cited by 2,498
Self-citationThe Hippo Signaling Pathway in Development and Cancer
Pan, D. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.09.011 · Cited by 2,317
Self-citationThe Hippo pathway and human cancer
Harvey, K. F., Zhang, X., & Thomas, D. M. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3458 · Cited by 1,867
Liu-Chittenden, Y., Huang, B., Shim, J. S., Chen, Q., Lee, S.-J., Anders, R. A., Liu, J. O., & Pan, D. (2012) · Genes & Development · doi:10.1101/gad.192856.112 · Cited by 1,452
Self-citationThe two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment
Johnson, R. L., & Halder, G. A. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4161 · Cited by 920
Structural Basis for the Autoinhibition of c-Abl Tyrosine Kinase
Nagar, B., Hantschel, O. D., Young, M. A., Scheffzek, K., Veach, D. R., Bornmann, W. G., Clarkson, B., Superti‐Furga, G., & Kuriyan, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00194-6 · Cited by 880
Metabolic control of YAP and TAZ by the mevalonate pathway
Sorrentino, G., Ruggeri, N., Specchia, V., Cordenonsi, M., Mano, M., Dupont, S., Manfrin, A., Ingallina, E., Sommaggio, R., Piazza, S., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb2936 · Cited by 776
Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signalling
Færgeman, N. J., & Knudsen, J. (1997) · Biochemical Journal · doi:10.1042/bj3230001 · Cited by 681
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The Hippo Signaling Pathway in Development and Disease
Zheng, Y., & Pan, D. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.06.003 · Cited by 867
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The Hippo signalling pathway and its implications in human health and diseases
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The role of lipids in cancer progression and metastasis
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Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies
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Metadata
- Authors
- Chan, P., Han, X., Zheng, B., DeRan, M., Yu, J., Jarugumilli, G. K., Deng, H., Pan, D., Luo, X., & Wu, X.
- Affiliations
- Harvard University (US)
- Jilin University (CN)
- Howard Hughes Medical Institute (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Luo, Xuelian
- Wu, Xu
- ORCID
- Venue
- Nature Chemical Biology
- Published
- 2016-02-22
- Volume
- 12
- Issue
- 4
- Pages
- 282-289
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC4798901
- OpenAlex
- W2274646531
- Cited by
- 313
- References
- 49
- Citations by year
- 2026: 40 · 2025: 38 · 2024: 54 · 2023: 37 · 2022: 39 · 2021: 21 · 2020: 26 · 2019: 19 · 2018: 21 · 2017: 13 · 2016: 4
- FWCI
- 13.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- U.S. Department of Defense (DE-AC02-06CH11357, R01CA181537, W81XWH, R01DK107651, W81XWH-13)
- Howard Hughes Medical Institute
- U.S. Department of Energy (DE‐ AC02‐06CH11357, AC02‐06CH11357, 06CH11357, DE-AC02-)
- Melanoma Research Alliance (R01CA181537, R01DK107651)
- University of Texas Southwestern Medical Center
- National Institutes of Health (DE-AC02–06CH11357, W81XWH)
- National Eye Institute (R01EY015708)
- National Cancer Institute (R01CA181537, DE-AC02-06CH11357)
- National Institute of General Medical Sciences (DE-AC02-06CH11357, R01GM107415)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK107651)
- Argonne National Laboratory (DE- AC02-06-CH11357, DE-AC02, AC02–06CH11357, 06CH11357)
- 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 › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- TEAD transcription factors, S-palmitoylation, Hippo signaling pathway, YAP, TAZ, VGLL4, protein lipidation, transcriptional regulation, myogenesis, tissue overgrowth, Yorkie, organ size control
- MeSH terms
- Hippo Signaling Pathway, YAP-Signaling Proteins, TEA Domain Transcription Factors, Amino Acid Sequence, Animals, Cell Differentiation, Cell Line, Cysteine, DNA-Binding Proteins, Fatty Acids, Unsaturated, Humans, Models, Molecular, Molecular Sequence Data, Nuclear Proteins, Palmitates, Protein Binding, Transcription Factors, Signal Transduction, Trans-Activators, Sequence Alignment, Conserved Sequence, Protein Serine-Threonine Kinases, Muscle Fibers, Skeletal, Protein Transport, Drosophila Proteins, Lipoylation
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