PathwayStep6302 PathwayStep6300 PathwayStep6301 PathwayStep6297 PathwayStep6296 PathwayStep6299 PathwayStep6298 PathwayStep6291 PathwayStep6290 PathwayStep6293 PathwayStep6292 PathwayStep6295 PathwayStep6294 PathwayStep6289 Bnip2 interacts with CDO complex Interaction of Bnip-2 with Cdc42 CDO binds BOC CDO binds promyogenic cadherins Interaction of p38 MAPK with JLP Activation of p38 alpha/beta MAPK JLP interacts with CDO complex Interaction of ABL1 with CDO complex Nuclear translocation of p38 MAPK Phosphorylation of E proteins by p38 MAPK Heterodimerization of E proteins with Myod Phosphorylation of MEF2 proteins by p38 Interaction of MyoD:E protein with MEF2 Neogenin:Netrin-3 binds CDO complex CDO in myogenesis Authored: Garapati, P V, 2008-08-11 10:36:48 CDO/Cdon (cell-adhesion-molecule-related/downregulated by oncogenes) is a type I transmembrane multifunctional co-receptor consisting of five immunoglobulin and three fibronectin type III (FNIII) repeats in the extracellular domain, and an intracellular domain with no identifiable motifs. It has been implicated in enhancing muscle differentiation in promyogenic cells. CDO exert its promyogenic effects as a component of multiprotein complexes that include the closely related factor Boc, the Ig superfamily receptor neogenin and its ligand netrin-3, and the adhesion molecules N- and M-cadherin. CDO modulates the Cdc42 and p38 mitogen-activated protein kinase (MAPK) pathways via a direct association with two scaffold-type proteins, JLP and Bnip-2, to regulate activities of myogenic bHLH factors and myogenic differentiation. CDO activates myogenic bHLH factors via enhanced heterodimer formation, most likely by inducing hyper-phosphorylation of E proteins. <br>Myogenic basic helix-loop-helix (bHLH) proteins are master regulatory proteins that activate the transcription of many muscle-specific genes during myogenesis. These myogenic bHLH proteins also referred to as MyoD family includes four members, MyoD, myogenin, myf5 and MRF4. These myogenic factors dimerize with E-proteins such as E12/E47, ITF-2 and HEB to form heterodimeric complexes that bind to a conserved DNA sequence known as the E box, which is present in the promoters and enhancers of most muscle-specific genes. Myocyte enhancer binding factor 2 (MEF2), which is a member of the MADS box family, also plays an important role in muscle differentiation. MEF2 activates transcription by binding to the consensus sequence, called the MEF2-binding site, which is also found in the control regions of numerous muscle-specific genes. MEF2 and myogenic bHLH proteins synergistically activate expression of muscle-specific genes via protein-protein interactions between DNA-binding domains of these heterologous classes of transcription factors. Members of the MyoD and MEF2 family of transcription factors associate combinatorially to control myoblast specification, differentiation and proliferation. Edited: Garapati, P V, 2008-08-11 10:36:48 GENE ONTOLOGYGO:0051149 Pubmed15923648 Reactome Database ID Release 43375170 Reactome, http://www.reactome.org ReactomeREACT_21402 Reviewed: Krauss, RS, 2010-02-09