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Significance The Hippo signaling pathway regulates cell proliferation in response to cell contact and a variety of other extracellular stimuli. It controls the activity and nuclear localization of cotranscriptional activator YAP, which interacts with DNA binding transcription factor TEAD, for the expression of target genes involved in cell proliferation. We show here that the expression level and transcriptional activity of TEAD are actively controlled by cell density through the modulation of its palmitoylation status. TEAD palmitoylation is controlled via fatty acid synthase and depalmitoylases in response to cell density. Our study indicates that the regulation of palmitoylation status is a potential target for controlling TEAD-dependent processes, perhaps including cancer growth.

Cell contact and Nf2/Merlin-dependent regulation of TEAD palmitoylation and activity