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Full-Text Articles in Translational Medical Research
Ixazomib Enhances Parathyroid Hormone-Induced Β-Catenin/T-Cell Factor Signaling By Dissociating Β-Catenin From The Parathyroid Hormone Receptor., Yanmei Yang, Hong Lei, Ya-Wei Qiang, Bin Wang
Ixazomib Enhances Parathyroid Hormone-Induced Β-Catenin/T-Cell Factor Signaling By Dissociating Β-Catenin From The Parathyroid Hormone Receptor., Yanmei Yang, Hong Lei, Ya-Wei Qiang, Bin Wang
Center for Translational Medicine Faculty Papers
The anabolic action of PTH in bone is mostly mediated by cAMP/PKA and Wnt-independent activation of β-catenin/T-cell factor (TCF) signaling. β-Catenin switches the PTH receptor (PTHR) signaling from cAMP/PKA to PLC/PKC activation by binding to the PTHR. Ixazomib (Izb) was recently approved as the first orally administered proteasome inhibitor for the treatment of multiple myeloma; it acts in part by inhibition of pathological bone destruction. Proteasome inhibitors were reported to stabilize β-catenin by the ubiquitin-proteasome pathway. However, how Izb affects PTHR activation to regulate β-catenin/TCF signaling is poorly understood. In the present study, using CRISPR/Cas9 genome-editing technology, we show that …