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Publication : Cross-talk between NR4A orphan nuclear receptors and β-catenin signaling pathway in osteoblasts.

First Author  Rajalin AM Year  2011
Journal  Arch Biochem Biophys Volume  509
Issue  1 Pages  44-51
PubMed ID  21362399 Mgi Jnum  J:177898
Mgi Id  MGI:5296449 Doi  10.1016/j.abb.2011.02.018
Citation  Rajalin AM, et al. (2011) Cross-talk between NR4A orphan nuclear receptors and beta-catenin signaling pathway in osteoblasts. Arch Biochem Biophys 509(1):44-51
abstractText  The canonical Wnt signaling pathway and its key mediator beta-catenin are important regulators of osteoblast function. NR4A orphan nuclear receptors (Nurr1, NGFI-B, and Nor1) are expressed in osteoblasts and have been shown to regulate the expression of osteoblastic genes and osteoblastic differentiation. Recently, interplay between Nurr1 and the canonical Wnt signaling pathway was reported in 293F cells. We have studied the potential interplay between NR4A receptors and beta-catenin in osteoblasts. NR4A receptors repressed beta-catenin-mediated transactivation when cotransfected in U2-OS cells. In addition, Nurr1 inhibited beta-catenin-mediated expression of Axin2 in MC3T3-E1 cells. The repression involved the DNA-binding domain of NR4A receptors. The repression of beta-catenin did not result from reduced beta-catenin expression or direct protein-protein interaction between beta-catenin and NR4A receptors. beta-Catenin was capable of inhibiting the transcriptional activity of NR4A receptors in U2-OS cells by a mechanism that involved the ligand-binding domain of NR4A receptors. As the canonical Wnt signaling pathway and beta-catenin are crucial for the development and function of osteoblasts, the repressive effect of NR4A receptors on beta-catenin is of potential biological and pathophysiological importance.
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