Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathway
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.
Chan P, Han X, Zheng B, DeRan M, Yu J, Jarugumilli GK, Deng H, Pan D, Luo X, Wu X.Yu H.
Another SBC Highlight:
Molecular mechanism of respiratory syncytial virus fusion inhibitors
Accurate chromosome segregation requires timely dissolution of chromosome cohesion after chromosomes are properly attached to the mitotic spindle. Separase is absolutely essential for cohesion dissolution in organisms from yeast to man.
SBC is pleased to announce the introduction of a Pilatus 3 X 6M detector into the User Program at beamline 19-ID.
Data collected by our users has been of outstanding quality.
19-BM Rebotic sample mounter available
A robot is now available for use at beamline 19-BM. The sample dewar accommodates ten Unipuck magazines; pins must be 18mm in length and use either SSRL or ALS bases. Experienced users may now request remote access to 19-BM when applying for beamtime.
Beginning August 01, 2015 the Midwest Center for Structural Genomics (MCSG) will start accepting applications for access to the MCSG User Resource.
MCSG's structure determination platform is well established, and combines technologies, robotics and expertise for gene cloning, protein production, and crystallization, as well as biochemical and biophysical characterization.