Transcriptional regulation by RUNX2 (Homo sapiens)

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16, 22, 23, 28, 50...168241039238, 62, 901341331011014613410122, 25, 37, 115, 141...3438, 6212617108447, 15911, 17, 24, 64, 66...555577, 805094, 171114611, 241347413494, 95168168133922692, 17277, 805, 1595094, 17138, 62, 901521341469519, 7215411, 17, 64, 66, 170172endoplasmic reticulum lumennucleoplasmcytosolITGBL1LGALS3 gene RUNX2-P2 CCNB1 RUNX2:SATB2Signaling by BMP6-Dehydrotestosterone RUNX2-P1 p-S463,S465-SMAD1 RUNX2-P2 CDKN1A genePPM1Dp-S451-RUNX2-P2 p-S196,T198,T200-RUNX2:CBFB:MMP13 genep-S183,T185,T187-RUNX2-P2 RUNX1:CBFB:LGALS3geneRUNX2-P1 SMAD4 TWIST2 UCMARBM14CBFB RUNX2-P2 p-S465-RUNX2-P1 SMAD4 RUNX2:SOX9RUNX2-P1 HEY2 RUNX2-P2 GLI3RHEY1,HEY2,HES1HEY1 RUNX2-P1 p-S465-RUNX2-P1 RUNX2-P2 RUNX2-P1 RB1 UCMA gene RUNX2:HAND2SP7 BGLAP genep-T309,S474-AKT2 RUNX2-P1 SOX9RUNX2:HDAC6LGALS3ITGA5(42-894)RUNX2:CBFB,p-S451-RUNX2:CBFB,(p-2S-RUNX2:CBFB)ITGBL1 gene p-Y-YAP1MyrG-p-Y419-SRC,MyrG-p-Y426-YES1p-T, p-S-AKTRUNX2-P2 CBFB DHTEST RUNX2-P2 p-S196,T198,T200-RUNX2-P1 RUNX2:CBFB:ITGA5genep-S432-RUNX2-P1 Hedgehog 'off' stateHEY2 CBFB HAND2p-T161-CDK1 HDAC6CBFB CBFB RUNX2:CBFB:p-2S-SMAD1:p-2S-SMAD1:SMAD4:SMAD6 geneBMP2 SMAD4 ATPHDAC6 p-S463,S465-SMAD1 RUNX2-P2 RUNX2-P1 GLI3R CBFB WWTR1 CBFB MMP13ADPRegulation of RUNX2expression andactivityRUNX2:ZNF521:HDAC3p-Y-YAP1 RUNX2-P2 RUNX2-P2 LGALS3 gene RUNX2-P1 RBM14 CDK4 BAX gene MAF MMP13 gene RUNX2-P2 p-Y-YAP1p-S294,S312-RUNX2-P1 CDKN1AMAF androst-4-en-3,17-dione SMAD6 gene HDAC3MyrG-p-Y419-SRC CCND1 2p-GLI2p-S451-RUNX2-P2 MAFRUNX2:RB1:BGLAP geneRUNX2-P1 p-S196,T198,T200-RUNX2:CBFBRUNX2-P2 RUNX2-P2 RUNX2-P1 UCMA geneCBFB RUNX2-P1 RUNX2:TWIST1,TWIST2RB1 CBFB RUNX2-P1 H2OSATB2 ITGA5 geneHedgehog 'on' stateCBFB RUNX2:CBFB:SP7:UCMAgenep-S196,T198,T200-RUNX2-P1 ZNF521 6-Dehydrotestosterone RUNX2:CBFB:p-2S-SMAD1:p-2S-SMAD1:SMAD4RUNX2:CBFB:IHH geneRUNX2:CBFB:p-Y-YAP1:BGLAP genep-S280,S298-RUNX2-P2 CCND1:CDK4p-S465-RUNX2-P1 RUNX2-P1 RUNX2-P1 RUNX2-P2 ATPRUNX2-P2 RUNX2-P1 p-S451-RUNX2-P2 RUNX2-P2 IHH genep-T202,Y204-MAPK3 CBFB SATB2RUNX2-P1 RUNX2:CBFB:ITGBL1geneMyrG-p-Y426-YES1 p-S294,S312-RUNX2-P1 MMP13 geneRUNX2-P1 RUNX2:2p-GLI2RUNX2-P2 SOX9 p-T185,Y187-MAPK1 RUNX2:RBM14BGLAP gene TEST p-S451-RUNX2-P2 p-S183,T185,T187-RUNX2-P2 COL1A1 gene RUNX2-P1 IHH gene p-S294,S312-RUNX2-P1 HAND2 RUNX2-P1 p-S451-RUNX2-P2 PPiCBFBATPRUNX2-P2 BGLAP gene androst-4-en-3,17-dione WWTR1p-T308,S473-AKT1 RUNX2RUNX2-P2 IHHRUNX2:MAFADPRUNX2-P1 TWIST2 RUNX2-P2 RUNX2-P1 BGLAP(24-100)CBFB p-S280,S298-RUNX2-P2 2p-GLI2 COL1A1RAF/MAP kinasecascadeCBFB p-T,Y MAPK dimersp-Y226,Y393-ABL1p-T305,S472-AKT3 RUNX2-P2 p-S451-RUNX2:CBFBRUNX2:CBFB:BAX geneTWIST1 RUNX2-P1 TWIST1,TWIST2MyrG-p-Y419-SRC,MyrG-p-Y426-YES1:YAP1RUNX2-P1 p-2S-SMAD1:p-2S-SMAD1:SMAD4RUNX2:CBFB,p-S451-RUNX2:CBFB,(p-2S-RUNX2:CBFB):BGLAP geneRUNX2-P2 CBFB RUNX2:WWTR1:BGLAPgeneRUNX2-P2 RUNX1 RUNX2:MAF:BGLAP geneDHTEST RUNX2-P2 HDAC6 p-S280,S298-RUNX2-P2 RUNX2-P2 RUNX2:GLI3RZNF521BAX geneBAXRUNX2-P2 RUNX2-P1 BGLAP gene HES1 ADPSignaling by NOTCH1RUNX2:HDAC4YAP1 CBFB AR:androgenHES1 HDAC4 CBFB Transcriptionalregulation by RUNX1p-S418-RUNX2-P2 RB1RUNX2-P2 SMAD6SMAD6 geneRUNX2-P1 RUNX2-P1 CCNB1:p-T161-CDK1RUNX2:AR:androgenp-S463,S465-SMAD1 (p-S451-RUNX2:CBFB,RUNX2:CBFB,RUNX2:HDAC6):CDKN1A geneWWTR1 RUNX2:WWTR1(TAZ)RB1 ADPBMP2 dimerHDAC4HDAC6 RUNX2:CBFBRUNX2-P2 RUNX2-P2 CBFB (p-S451-RUNX2:CBFB,RUNX2:CBFB,RUNX2:HDAC6)RUNX2:HEY1,HEY2,HES1CBFB HEY1 BGLAP gene RUNX2-P2 p-S465-RUNX2-P1 RUNX2:CBFB:LGALS3geneBGLAP gene RUNX2:RB1:COL1A1geneCBFB AR ATPRUNX2-P1 MyrG-p-Y426-YES1 ITGBL1 geneLGALS3 geneRUNX2:RB1RUNX2-P1 RUNX2-P2 SP7RUNX2-P1 RUNX2-P1 RUNX2-P2 MyrG-p-Y419-SRC RUNX2-P1 ITGA5 gene AR TWIST1 RUNX2-P2 p-2S-RUNX2:CBFBp-S432-RUNX2:CBFBHDAC3 CBFB RUNX2-P1 p-Y-YAP1 TEST RUNX2-P1 RUNX2-P1 CBFB RUNX2:CBFB:p-Y-YAP1RUNX2-P1 YAP1RUNX2-P2 RUNX2-P2 p-S465-RUNX2-P1 CDKN1A gene COL1A1 gene7410116813415922, 28, 29, 41, 43...101841468095134468, 15, 104, 1101342295170168133558, 15, 104, 110241, 3, 6, 20, 31...802, 4, 7, 9, 13...12, 6530, 36, 53, 54, 68...1261190154


RUNX2 (CBFA1 or AML3) transcription factor, similar to other RUNX family members, RUNX1 and RUNX3, can function in complex with CBFB (CBF-beta) (Kundu et al. 2002, Yoshida et al. 2002, Otto et al. 2002). RUNX2 mainly regulates transcription of genes involved in skeletal development (reviewed in Karsenty 2008). RUNX2 is involved in development of both intramembraneous and endochondral bones through regulation of osteoblast differentiation and chondrocyte maturation, respectively. RUNX2 stimulates transcription of the BGLAP gene (Ducy and Karsenty 1995, Ducy et al. 1997), which encodes Osteocalcin, a bone-derived hormone which is one of the most abundant non-collagenous proteins of the bone extracellular matrix (reviewed in Karsenty and Olson 2016). RUNX2 directly controls the expression of most genes associated with osteoblast differentiation and function (Sato et al. 1998, Ducy et al. 1999, Roce et al. 2005). RUNX2-mediated transcriptional regulation of several genes involved in GPCR (G protein coupled receptor) signaling is implicated in the control of growth of osteoblast progenitors (Teplyuk et al. 2009). RUNX2 promotes chondrocyte maturation by stimulating transcription of the IHH gene, encoding Indian hedgehog (Takeda et al. 2001, Yoshida et al. 2004). Germline loss-of-function mutations of the RUNX2 gene are associated with cleidocranial dysplasia syndrome (CCD), an autosomal skeletal disorder (reviewed in Jaruga et al. 2016). The function of RUNX2 is frequently disrupted in osteosarcoma (reviewed in Mortus et al. 2014). Vitamin D3 is implicated in regulation of transcriptional activity of the RUNX2:CBFB complex (Underwood et al. 2012).

RUNX2 expression is regulated by estrogen signaling, and RUNX2 is implicated in breast cancer development and metastasis (reviewed in Wysokinski et al. 2014). Besides estrogen receptor alpha (ESR1) and estrogen-related receptor alpha (ERRA) (Kammerer et al. 2013), RUNX2 transcription is also regulated by TWIST1 (Yang, Yang et al. 2011), glucocorticoid receptor (NR3C1) (Zhang et al. 2012), NKX3-2 (BAPX1) (Tribioli and Lufkin 1999, Lengner et al. 2005), DLX5 (Robledo et al. 2002, Lee et al. 2005) and MSX2 (Lee et al. 2005). RUNX2 can autoregulate, by directly inhibiting its own transcription (Drissi et al. 2000). Several E3 ubiquitin ligases target RUNX2 for proteasome-mediated degradation: FBXW7a (Kumar et al. 2015), STUB1 (CHIP) (Li et al. 2008), SMURF1 (Zhao et al. 2003, Yang et al. 2014), WWP1 (Jones et al. 2006), and SKP2 (Thacker et al. 2016). Besides formation of RUNX2:CBFB heterodimers, transcriptional activity of RUNX2 is regulated by binding to a number of other transcription factors, for example SOX9 (Zhou et al. 2006, TWIST1 (Bialek et al. 2004) and RB1 (Thomas et al. 2001).<p>RUNX2 regulates expression of several genes implicated in cell migration during normal development and bone metastasis of breast cancer cells. RUNX2 stimulates transcription of the ITGA5 gene, encoding Integrin alpha 5 (Li et al. 2016) and the ITGBL1 gene, encoding Integrin beta like protein 1 (Li et al. 2015). RUNX2 mediated transcription of the MMP13 gene, encoding Colagenase 3 (Matrix metalloproteinase 13), is stimulated by AKT mediated phosphorylation of RUNX2 (Pande et al. 2013). RUNX2 is implicated in positive regulation of AKT signaling by stimulating expression of AKT-activating TORC2 complex components MTOR and RICTOR, which may contribute to survival of breast cancer cells (Tandon et al. 2014).<p>RUNX2 inhibits CDKN1A transcription, thus preventing CDKN1A-induced cell cycle arrest. Phosphorylation of RUNX2 by CDK4 in response to high glucose enhances RUNX2-mediated repression of the CDKN1A gene in endothelial cells (Pierce et al. 2012). In mice, Runx2-mediated repression of Cdkn1a may contribute to the development of acute myeloid leukemia (AML) (Kuo et al. 2009). RUNX2 can stimulate transcription of the LGALS3 gene, encoding Galectin-3 (Vladimirova et al. 2008, Zhang et al. 2009). Galectin 3 is expressed in myeloid progenitors and its levels increase during the maturation process (Le Marer 2000).<p>For a review of RUNX2 function, please refer to Long 2012 and Ito et al. 2015. View original pathway at:Reactome.</div>


Pathway is converted from Reactome ID: 8878166
Reactome version: 66
Reactome Author 
Reactome Author: Orlic-Milacic, Marija

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