Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress transcription
Department of Cell Biology; Graduate School of Biomedical Sciences
Life Sciences | Medicine and Health Sciences
Src/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.
DOI of Published Version
EMBO J. 2004 Feb 25;23(4):790-9. Epub 2004 Feb 12. Link to article on publisher's site
The EMBO journal
Zaidi SK, Sullivan AJ, Medina RF, Ito Y, Van Wijnen AJ, Stein JL, Lian JB, Stein GS. (2004). Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress transcription. GSBS Student Publications. https://doi.org/10.1038/sj.emboj.7600073. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/709