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

259 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Phosphorylation
Transcription
Tyrosine
src-Family Kinases
Osteocalcin
Osteoblasts
Proteins
Core Binding Factor Alpha 1 Subunit
Genes
Co-Repressor Proteins
Gene expression
Protein-Tyrosine Kinases
Bone
Homeostasis
Transcription Factors
Phosphotransferases
Gene Expression
Bone and Bones

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Zaidi, S. K., Sullivan, A. J., Medina, R., Ito, Y., van Wijnen, A. J., Stein, J. L., ... 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

Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress transcription. / Zaidi, Sayyed K.; Sullivan, Andrew J.; Medina, Ricardo; Ito, Yoshiaki; van Wijnen, Andre J; Stein, Janet L.; Lian, Jane B.; Stein, Gary S.

In: EMBO Journal, Vol. 23, No. 4, 25.02.2004, p. 790-799.

Research output: Contribution to journalArticle

Zaidi, SK, Sullivan, AJ, Medina, R, Ito, Y, van Wijnen, AJ, Stein, JL, Lian, JB & Stein, GS 2004, 'Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress transcription', EMBO Journal, vol. 23, no. 4, pp. 790-799. https://doi.org/10.1038/sj.emboj.7600073
Zaidi SK, Sullivan AJ, Medina R, Ito Y, van Wijnen AJ, Stein JL et al. Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress transcription. EMBO Journal. 2004 Feb 25;23(4):790-799. https://doi.org/10.1038/sj.emboj.7600073
Zaidi, Sayyed K. ; Sullivan, Andrew J. ; Medina, Ricardo ; Ito, Yoshiaki ; van Wijnen, Andre J ; Stein, Janet L. ; Lian, Jane B. ; Stein, Gary S. / Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress transcription. In: EMBO Journal. 2004 ; Vol. 23, No. 4. pp. 790-799.
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