Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma

• Published in: Nature communications Vol. 11; no. 1; pp. 1931 - 14
• Main Authors: Huang, Hector H., Ferguson, Ian D., Thornton, Alexis M., Bastola, Prabhakar, Lam, Christine, Lin, Yu-Hsiu T., Choudhry, Priya, Mariano, Margarette C., Marcoulis, Makeba D., Teo, Chin Fen, Malato, Julia, Phojanakong, Paul J., Martin, Thomas G., Wolf, Jeffrey L., Wong, Sandy W., Shah, Nina, Hann, Byron, Brooks, Angela N., Wiita, Arun P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.04.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/109; 14/19; 38/91; 59/5; 631/1647/296; 631/1647/514/1949; 631/45/475; 631/45/475/2290; 631/67/1990; 64/60; 82/58; Alternative splicing; Animals; Anticancer properties; Antineoplastic Agents - administration & dosage; Antitumor agents; Female; Gene expression; Homeostasis; Humanities and Social Sciences; Humans; Inhibitors; Interference; Mice; Modulation; multidisciplinary; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - genetics; Multiple Myeloma - metabolism; Oligopeptides - administration & dosage; Phosphorylation; Proteasome inhibitors; Proteasome Inhibitors - administration & dosage; Proteins; Ribonucleic acid; RNA; RNA Splicing - drug effects; Science; Science (multidisciplinary); Spliceosomes - drug effects; Spliceosomes - genetics; Spliceosomes - metabolism; Spliceosomes - microbiology; Splicing

Enhancing the efficacy of proteasome inhibitors (PI) is a central goal in myeloma therapy. We proposed that signaling-level responses after PI may reveal new mechanisms of action that can be therapeutically exploited. Unbiased phosphoproteomics after treatment with the PI carfilzomib surprisingly de...