{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:47:14Z","timestamp":1786978034608,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,4,13]],"date-time":"2009-04-13T00:00:00Z","timestamp":1239580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2009,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Proteasome inhibitors represent a promising therapy for the treatment of relapsed and\/or refractory multiple myeloma, a disease that is concomitant with osteolysis and enhanced osteoclast formation. While blockade of the proteosome pathway has been recently shown to influence osteoclast formation and function, the precise molecular cascade underlying these effects is presently unclear. Here, we provide evidence that proteasome inhibitors directly impair osteoclast formation and function via the disruption of key RANK\u2010mediated signaling cascades. Disruption of the proteosome pathway using selective inhibitors (MG\u2010132, MG\u2010115, and epoxomicin) resulted in the accumulation of p62 and CYLD, and altered the subcellular targeting and distribution of p62 and TRAF6 in osteoclast\u2010like cells. Proteosome inhibition also blocked RANKL\u2010induced NF\u2010\u03baB activation, I\u03baB\u03b1 degradation and nuclear translocation of p65. The disruption in RANK\u2010signaling correlated dose\u2010dependently with an impairment in osteoclastogenesis, with relative potency epoxomicin\u2009&gt;\u2009MG\u2010132\u2009&gt;\u2009MG\u2010115 based on equimolar concentrations. In addition, these inhibitors were found to impact osteoclastic microtubule organization and attenuate bone resorption. Based on these data we propose that deregulation of key RANK\u2010mediated signaling cascades (p62, TRAF6, CYLD, and I\u03baB\u03b1) underscores proteasome\u2010mediated inhibition of osteolytic bone conditions. J. Cell. Physiol. 220: 450\u2013459, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21787","type":"journal-article","created":{"date-parts":[[2009,4,13]],"date-time":"2009-04-13T09:30:24Z","timestamp":1239615024000},"page":"450-459","source":"Crossref","is-referenced-by-count":64,"title":["Proteasome inhibitors impair RANKL\u2010induced NF\u2010\u03baB activity in osteoclast\u2010like cells via disruption of p62, TRAF6, CYLD, and I\u03baB\u03b1 signaling cascades"],"prefix":"10.1002","volume":"220","author":[{"given":"Estabelle","family":"Ang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan J.","family":"Pavlos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah 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