Scientific background: |
RELB(v-rel reticuloendotheliosis viral oncogene homolog B) is also known as IREL. The International Radiation Hybrid Mapping Consortium assigned the RELB gene to chromosome 19. By RT-PCR and immunocytochemical analyses, Clark et al. (1999) showed that RELB expression correlated with dendritic cell activation.NF-kappa-B-inducing kinase is required for osteoclastogenesis in response to pathologic stimuli. Vaira et al. (2008) found that overexpression of Relb, but not Rela, rescued differentiation of mouse Nik -/- osteoclast precursors, indicating that blockade of the alternative NF-kappa-B pathway, rather than the classical NF-kappa-B pathway, is responsible for the osteoclastogenic defect in the absence of Nik. Using Relb -/- mice, they showed that Relb itself was required for Rankl-induced osteoclastogenesis in vitro and for TNF-induced bone resorption in vivo. Both Relb -/- and Nik -/- mice were resistant to tumor-mediated osteolysis. Vaira et al. (2008) concluded that the alternative NF-kappa-B pathway, via RELB, plays an essential and unique role in RANKL signaling toward osteoclast development. |
References: |
1. Clark, G. J., Gunningham, S., Troy, A., Vuckovic, S., Hart, D. N.Expression of the RelB transcription factor correlates with the activation of human dendritic cells.Immunology 98: 189-196, 1999.
2. Ruben, S. M., Klement, J. F., Coleman, T. A., Maher, M., Chen, C.-H., Rosen, C. A.I-Rel: a novel rel-related protein that inhibits NF-kappa-B transcriptional activity.Genes Dev. 6: 745-760, 1992.
3. Vaira, S., Johnson, T., Hirbe, A. C., Alhawagri, M., Anwisye, I., Sammut, B., O'Neal, J., Zou, W., Weilbaecher, K. N., Faccio, R., Novack, D. V. RelB is the NF-kappa-B subunit downstream of NIK responsible for osteoclast differentiation.Proc. Nat. Acad. Sci. 105: 3897-3902, 2008. |