Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress transcription

Sayyed K. Zaidi, Andrew J. Sullivan, Ricardo Medina, Yoshiaki Ito, Andre J. Van Wijnen, Janet L. Stein, Jane B. Lian, Gary S. Stein

Research output: Contribution to journalArticle

269 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)790-799
Number of pages10
JournalEMBO Journal
Volume23
Issue number4
DOIs
StatePublished - Feb 25 2004

Keywords

  • Cbfa1
  • Nuclear matrix
  • Osteoblasts
  • Osteocalcin
  • Src signaling

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Zaidi, S. K., Sullivan, A. J., Medina, R., Ito, Y., Van Wijnen, A. J., Stein, J. L., Lian, J. B., & Stein, G. S. (2004). Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress transcription. EMBO Journal, 23(4), 790-799. https://doi.org/10.1038/sj.emboj.7600073