RUNX2 binds HEY1,HEY2,HES1

Stable Identifier
R-HSA-9008177
Type
Reaction [binding]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
RUNX2 binds HEY1,HEY2,HES1
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Based on studies in mice, RUNX2 forms a complex with HEY2 (HRT2), a product of the NOTCH1 target gene. Binding to HEY2 inhibits RUNX2-mediated transcriptional activation of the BGLAP (Osteocalcin) gene (Garg et al. 2005). Other NOTCH1 targets, HEY1 and HES1, can also bind to RUNX2 and inhibit RUNX2 transcriptional activity (Hilton et al. 2008). NOTCH1 mutations cause severe aortic valve calcification in humans, which may be due to impaired repression of RUNX2-mediated transcription (Garg et al. 2005). NOTCH-mediated inhibition of RUNX2 transcriptional activity is also implicated in the maintenance of mesenchymal progenitors in the bone marrow by suppression of osteoblast differentiation (Hilton et al. 2008).

NOTCH1 may also inhibit RUNX2-mediated activation of target promoters by formation of a complex between RUNX2 and NOTCH1 intracellular domain (NICD1) (Engin et al. 2008).

Literature References
PubMed ID Title Journal Year
16025100 Mutations in NOTCH1 cause aortic valve disease

Ransom, JF, Muth, AN, Grossfeld, PD, Barnes, R, Schluterman, MK, Garg, V, Srivastava, D, King, IN

Nature 2005
Participants
Input
Output
Participates
as an event of
Inferred From
Runx2 binds Hey1,Hey2,Hes1 (Mus musculus)
Authored
Orlic-Milacic, M  (2017-06-08)
Reviewed
Ducy, P  (2017-08-04)
Created
Orlic-Milacic, M  (2017-06-07)
Cite Us!