期刊
EMBO JOURNAL
卷 23, 期 4, 页码 790-799出版社
WILEY
DOI: 10.1038/sj.emboj.7600073
关键词
Cbfa1; nuclear matrix; osteoblasts; osteocalcin; Src signaling
资金
- NCI NIH HHS [P01 CA082834, P01 CA82834] Funding Source: Medline
- NIAMS NIH HHS [P01 AR48818, AR39588, P01 AR048818, R01 AR049069] Funding Source: Medline
- NIDCR NIH HHS [DE12528, R37 DE012528, R01 DE012528] Funding Source: Medline
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.
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