6rk1

Structural highlights

Function

[CCN3_RAT] Immediate-early protein playing a role in various cellular processes including proliferation, adhesion, migration, differentiation and survival. Acts by binding to integrins or membrane receptors such as NOTCH1. Essential regulator of hematopoietic stem and progenitor cell function. Inhibits myogenic differentiation through the activation of Notch-signaling pathway. Inhibits vascular smooth muscle cells proliferation by increasing expression of cell-cycle regulators such as CDKN2B or CDKN1A independently of TGFB1 signaling. Ligand of integrins ITGAV:ITGB3 and ITGA5:ITGB1, acts directly upon endothelial cells to stimulate pro-angiogenic activities and induces angiogenesis. In endothelial cells, supports cell adhesion, induces directed cell migration (chemotaxis) and promotes cell survival. Plays also a role in cutaneous wound healing acting as integrin receptor ligand. Supports skin fibroblast adhesion through ITGA5:ITGB1 and ITGA6:ITGB1 and induces fibroblast chemotaxis through ITGAV:ITGB5. Seems to enhance bFGF-induced DNA synthesis in fibroblasts (By similarity). Involved in bone regeneration as a negative regulator (By similarity). Enhances the articular chondrocytic phenotype, whereas it repressed the one representing endochondral ossification (PubMed:21871891). Impairs pancreatic beta-cell function, inhibits beta-cell proliferation and insulin secretion (By similarity). Plays a role as negative regulator of endothelial pro-inflammatory activation reducing monocyte adhesion, its anti-inflammatory effects occur secondary to the inhibition of NF-kappaB signaling pathway (By similarity). Contributes to the control and coordination of inflammatory processes in atherosclerosis (By similarity). Attenuates inflammatory pain through regulation of IL1B- and TNF-induced MMP9, MMP2 and CCL2 expression. Inhibits MMP9 expression through ITGB1 engagement (PubMed:22353423).[UniProtKB:P48745][UniProtKB:Q64299]^{[1] [2]}

References

1. ↑ Janune D, Kubota S, Nishida T, Kawaki H, Perbal B, Iida S, Takigawa M. Novel effects of CCN3 that may direct the differentiation of chondrocytes. FEBS Lett. 2011 Oct 3;585(19):3033-40. doi: 10.1016/j.febslet.2011.08.024. Epub, 2011 Aug 23. PMID:21871891 doi:http://dx.doi.org/10.1016/j.febslet.2011.08.024
2. ↑ Kular L, Rivat C, Lelongt B, Calmel C, Laurent M, Pohl M, Kitabgi P, Melik-Parsadaniantz S, Martinerie C. NOV/CCN3 attenuates inflammatory pain through regulation of matrix metalloproteinases-2 and -9. J Neuroinflammation. 2012 Feb 21;9:36. doi: 10.1186/1742-2094-9-36. PMID:22353423 doi:http://dx.doi.org/10.1186/1742-2094-9-36