Nature Communications (Apr 2020)
Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma
- Hector H. Huang,
- Ian D. Ferguson,
- Alexis M. Thornton,
- Prabhakar Bastola,
- Christine Lam,
- Yu-Hsiu T. Lin,
- Priya Choudhry,
- Margarette C. Mariano,
- Makeba D. Marcoulis,
- Chin Fen Teo,
- Julia Malato,
- Paul J. Phojanakong,
- Thomas G. Martin,
- Jeffrey L. Wolf,
- Sandy W. Wong,
- Nina Shah,
- Byron Hann,
- Angela N. Brooks,
- Arun P. Wiita
Affiliations
- Hector H. Huang
- Department of Laboratory Medicine, University of California
- Ian D. Ferguson
- Department of Laboratory Medicine, University of California
- Alexis M. Thornton
- Department of Biomolecular Engineering, University of California
- Prabhakar Bastola
- Department of Laboratory Medicine, University of California
- Christine Lam
- Department of Laboratory Medicine, University of California
- Yu-Hsiu T. Lin
- Department of Laboratory Medicine, University of California
- Priya Choudhry
- Department of Laboratory Medicine, University of California
- Margarette C. Mariano
- Department of Laboratory Medicine, University of California
- Makeba D. Marcoulis
- Department of Laboratory Medicine, University of California
- Chin Fen Teo
- Department of Physiology, University of California
- Julia Malato
- Helen Diller Family Comprehensive Cancer Center, University of California
- Paul J. Phojanakong
- Helen Diller Family Comprehensive Cancer Center, University of California
- Thomas G. Martin
- Helen Diller Family Comprehensive Cancer Center, University of California
- Jeffrey L. Wolf
- Helen Diller Family Comprehensive Cancer Center, University of California
- Sandy W. Wong
- Helen Diller Family Comprehensive Cancer Center, University of California
- Nina Shah
- Helen Diller Family Comprehensive Cancer Center, University of California
- Byron Hann
- Helen Diller Family Comprehensive Cancer Center, University of California
- Angela N. Brooks
- Department of Biomolecular Engineering, University of California
- Arun P. Wiita
- Department of Laboratory Medicine, University of California
- DOI
- https://doi.org/10.1038/s41467-020-15521-4
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 14
Abstract
The mechanisms of action of proteasome inhibitors (PI) in multiple myeloma (MM) treatment are not fully elucidated. Here, the authors use unbiased phosphoproteomics in PI-treated MM and show increased phosphorylation of splicing-associated proteins, ultimately revealing splicing interference as a mode of PI action as well as demonstrating the spliceosome as a specific therapeutic vulnerability in this disease.
