| First Author | Poblenz AT | Year | 2007 |
| Journal | Biochem Biophys Res Commun | Volume | 359 |
| Issue | 3 | Pages | 510-5 |
| PubMed ID | 17544369 | Mgi Jnum | J:122282 |
| Mgi Id | MGI:3713954 | Doi | 10.1016/j.bbrc.2007.05.151 |
| Citation | Poblenz AT, et al. (2007) Inhibition of RANKL-mediated osteoclast differentiation by selective TRAF6 decoy peptides. Biochem Biophys Res Commun 359(3):510-5 |
| abstractText | RANK and RANKL are essential mediators of osteoclastogenesis. RANK interacts with members of the tumor necrosis factor receptor-associated factor (TRAF) family, of which TRAF6 is the critical signaling molecule. We identified a unique TRAF6-binding motif in RANK, which was subsequently co-crystallized with TRAF6 revealing distinct molecular interactions. A cell-permeable TRAF6 decoy peptide (T6DP) was shown to specifically target TRAF6 and inhibit RANKL-mediated signaling. In this study, we identified a core motif for binding to TRAF6 by generating a series of deletion mutants linked via palmitate as a means to internalize the peptide, thus making a smaller scaffold for intracellular delivery. The core motif of RKIPTEDEY inhibited RANKL-mediated osteoclastogenesis and bone resorption. In contrast, TRAF2/5 decoy peptides appeared to have no affect. Thus, disruption of the RANK-TRAF6 interaction may prove useful as a novel target for the development of a small molecule therapeutic agent for the treatment of bone-related diseases. |
