Cell contact and Nf2/Merlin-dependent regulation of TEAD palmitoylation and activity
Identifieur interne : 000579 ( Ncbi/Checkpoint ); précédent : 000578; suivant : 000580Cell contact and Nf2/Merlin-dependent regulation of TEAD palmitoylation and activity
Auteurs : Nam-Gyun Kim ; Barry M. GumbinerSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2019.
Abstract
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.
Url:
DOI: 10.1073/pnas.1819400116
PubMed: 31043565
PubMed Central: 6525549
Affiliations:
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PMC:6525549Le document en format XML
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<affiliation><nlm:aff id="aff1">Center for Developmental Biology and Regenerative Medicine,<institution>Seattle Children’s Research Institute</institution>
, Seattle,<addr-line>WA</addr-line>
98101;</nlm:aff>
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<affiliation><nlm:aff id="aff2">Department of Pediatrics,<institution>University of Washington School of Medicine</institution>
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<affiliation><nlm:aff id="aff2">Department of Pediatrics,<institution>University of Washington School of Medicine</institution>
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<affiliation><nlm:aff id="aff3">Department of Biochemistry,<institution>University of Washington School of Medicine</institution>
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, Seattle,<addr-line>WA</addr-line>
98101;</nlm:aff>
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98195;</nlm:aff>
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<front><div type="abstract" xml:lang="en"><title>Significance</title>
<p>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.</p>
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