Combined TRAF6 Targeting and Proteasome Blockade Has Anti-myeloma and Anti-Bone Resorptive Effects

• Published in: Molecular cancer research Vol. 15; no. 5; pp. 598 - 609
• Main Authors: Chen, Haiming, Li, Mingjie, Sanchez, Eric, Wang, Cathy S., Lee, Tiffany, Soof, Camilia M., Casas, Christian E., Cao, Jasmin, Xie, Colin, Udd, Kyle A., DeCorso, Kevin, Tang, George Y., Spektor, Tanya M., Berenson, James R.
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 01.05.2017
• Subjects: Activation; Apoptosis; Biocompatibility; Biomedical materials; Bone loss; Bone marrow; Bone resorption; Bortezomib; Bortezomib - pharmacology; Cancer; CD14 antigen; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Dentin; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic - drug effects; Humans; I-kappa B Kinase - metabolism; Interleukin 1; Interleukin 1 receptors; JNK protein; Leukocytes (mononuclear); Monoclonal gammopathy; Monoclonal Gammopathy of Undetermined Significance - genetics; Monoclonal Gammopathy of Undetermined Significance - metabolism; Monocytes; Multiple myeloma; Multiple Myeloma - genetics; Multiple Myeloma - metabolism; NF-κB protein; Oligopeptides - pharmacology; Patients; Peptides; Peptides - pharmacology; Proteasome inhibitors; Remission; Signal transduction; Signal Transduction - drug effects; Signaling; TNF Receptor-Associated Factor 6 - antagonists & inhibitors; TNF Receptor-Associated Factor 6 - genetics; TNF Receptor-Associated Factor 6 - metabolism; TRAF6 protein; TRANCE protein; Tumor cells; Tumor necrosis factor; Tumor necrosis factor receptors; Ubiquitination - drug effects; Up-Regulation

TNF receptor–associated factor 6 (TRAF6) has been implicated in polyubiquitin-mediated IL1R/TLR signaling through activation of IκB kinase (IKK) to regulate the NF-κB and JNK signaling pathways. Here, TRAF6 protein was determined to be overexpressed in bone marrow mononuclear cells (BMMC) from patie...