Journal
NATURE CHEMICAL BIOLOGY
Volume 12, Issue 4, Pages 282-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEMBIO.2036
Keywords
-
Categories
Funding
- Stewart Rahr-MRA (Melanoma Research Alliance) Young Investigator Award
- Department of Defense (DoD) Career Development Award [W81XWH-13-1-0203]
- American Cancer Society [124929-RSG-13-291-01-TBE]
- US National Institutes of Health/National Cancer Institute [R01CA181537]
- National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [R01DK107651-01]
- National Institutes of Health/National Institute of General Medical Sciences [R01GM107415]
- National Institute of Health/National Eye Institute [R01EY015708]
- Howard Hughes Medical Institute
- US Department of Energy (DOE) [DE-AC02-06CH11357]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available