ArticleThe Journal of biological chemistry2010
FGF2-activated ERK mitogen-activated protein kinase enhances Runx2 acetylation and stabilization.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 122 citations in OpenAlex.
- Vascular calcification: pathogenic mechanisms, signaling crosstalk and translational therapeutics.Signal transduction and targeted therapy · 2026Review
- CaMKIV negatively regulates osteoblast differentiation by modulating c-Fos and NFATc1 signaling: an in vitro and in vivo mechanistic study.BMB reports · 2026Article
- Runx2 acetylation enhances pulmonary inflammation in chronic obstructive pulmonary disease through activating CDK8.Respiratory research · 2026Article
- Review
- Therapeutic potential of hAMSCs in ligament regeneration: insights from the UCA1-miR-16-5p-FGF2 pathway.Stem cell research & therapy · 2025Article
- The dual roles of peptidoglycans: NOD1 and NOD2 inversely regulate bone metabolism.Experimental & molecular medicine · 2025Article
- Targeted allele-specificMolecular therapy. Nucleic acids · 2025Article
- Investigation of the osteogenic effects of ICA and ICSII on rat bone marrow mesenchymal stem cells.Scientific reports · 2025Article
- Mettl1-mediated mInternational journal of biological sciences · 2025Article
- Dopamine promotes osteogenic differentiation of PDLSCs by activating DRD1 and DRD2 during orthodontic tooth movement via ERK1/2 signaling pathway.Regenerative therapy · 2024Article
- Regulation of Skeletal Development and Maintenance by Runx2 and Sp7.International journal of molecular sciences · 2024Review
- Citric Acid: A Nexus Between Cellular Mechanisms and Biomaterial Innovations.Advanced materials (Deerfield Beach, Fla.) · 2024Review
- Inhibition of RIPK1 alleviating vascular smooth muscle cells osteogenic transdifferentiation via Runx2.iScience · 2024Article
- Bone-derived PDGF-BB drives brain vascular calcification in male mice.The Journal of clinical investigation · 2023Article
- Peptidylarginine deiminase 2 plays a key role in osteogenesis by enhancing RUNX2 stability through citrullination.Cell death & disease · 2023Article
- Nicotinamide enhances osteoblast differentiation through activation of the mitochondrial antioxidant defense system.Experimental & molecular medicine · 2023Article
- Butyrate potentiates Enterococcus faecalis lipoteichoic acid-induced inflammasome activation via histone deacetylase inhibition.Cell death discovery · 2023Article
- A miR-125/Sirtuin-7 pathway drives the pro-calcific potential of myeloid cells in diabetic vascular disease.Diabetologia · 2022Article
- Whole Aspect of Runx2 Functions in Skeletal Development.International journal of molecular sciences · 2022Review
- Excessive osteoclast activation by osteoblast paracrine factor RANKL is a major cause of the abnormal long bone phenotype in Apert syndrome model mice.Journal of cellular physiology · 2022Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Runx2 is a key transcription factor regulating osteoblast differentiation and skeletal morphogenesis, and FGF2 is one of the most important regulators of skeletal development. The importance of the ERK mitogen-activated protein (MAP) kinase pathway in cranial suture development was demonstrated by the findings that the inhibition of FGF/FGF receptor (FGFR) signaling by a MEK blocker prevents the premature suture closure caused by an Fgfr2 mutation in mice. We previously demonstrated that ERK activation does not affect Runx2 gene expression but that it stimulates Runx2 transcriptional activity. However, the molecular mechanism underlying Runx2 activation by FGF/FGFR or ERK was still unclear. In this study, we found that FGF2 treatment increased the protein level of exogenously overexpressed Runx2 and that this increase is reversed by ERK inhibitors. In contrast, overexpression of constitutively active MEK strongly increased the Runx2 protein level, which paralleled an increase in Runx2 acetylation. As Runx2 protein phosphorylation mediated by ERK directly correlates with Runx2 protein stabilization, acetylation, and ubiquitination, we undertook to identify the ERK-dependent phosphorylation sites in Runx2. Analysis of two C-terminal Runx2 deletion constructs showed that the middle third of the protein is responsible for ERK-induced stabilization and activation. An in silico analysis of highly conserved ERK targets indicated that there are three relevant serine residues in this domain. Site-directed mutagenesis implicated Ser-301 in for ERK-mediated Runx2 stabilization and acetylation. In conclusion, the FGF2-induced ERK MAP kinase strongly increased the Runx2 protein level through an increase in acetylation and a decrease in ubiquitination, and these processes require the phosphorylation of Runx2 Ser-301 residue.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.