Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress transcription
AuthorsZaidi, Sayyed K.
Sullivan, Andrew J.
Medina, Ricardo F.
Van Wijnen, Andre J.
Stein, Janet L.
Lian, Jane B.
Stein, Gary S.
KeywordsAmino Acid Motifs; Animals; Cell Line, Tumor; Cell Nucleus; Chromatin; Core Binding Factor Alpha 1 Subunit; DNA-Binding Proteins; Humans; Nuclear Proteins; Osteoblasts; Osteocalcin; Phosphorylation; Rats; Signal Transduction; Trans-Activators; Transcription Factor AP-2; Transcription Factors; Transcription, Genetic; Tyrosine; src-Family Kinases
Medicine and Health Sciences
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AbstractSrc/Yes tyrosine kinase signaling contributes to the regulation of bone homeostasis and inhibits osteoblast activity. Here we show that the endogenous Yes-associated protein (YAP), a mediator of Src/Yes signaling, interacts with the native Runx2 protein, an osteoblast-related transcription factor, and suppresses Runx2 transcriptional activity in a dose-dependent manner. Runx2, through its PY motif, recruits YAP to subnuclear domains in situ and to the osteocalcin (OC) gene promoter in vivo. Inhibition of Src/Yes kinase blocks tyrosine phosphorylation of YAP and dissociates endogenous Runx2-YAP complexes. Consequently, recruitment of the YAP co-repressor to subnuclear domains is abrogated and expression of the endogenous OC gene is induced. Our results suggest that Src/Yes signals are integrated through organization of Runx2-YAP transcriptional complexes at subnuclear sites to attenuate skeletal gene expression.
SourceEMBO J. 2004 Feb 25;23(4):790-9. Epub 2004 Feb 12. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/34061
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