Functional genetics reveals modulators of antimicrotubule drug sensitivity
Name
jcb_202403065.pdf
Description
Published version
Size
5.33 MB
Format
Adobe PDF
Checksum (MD5)
c7cf4b322ea1b3c8e10828488546a426
Author(s)
Su, Kuan-Chung
Radul, Elena
Maier, Nolan K
Tsang, Mary-Jane
Goul, Claire
Moodie, Brittania
Marescal, Océane
Keys, Heather R
Cheeseman, Iain M
Date Issued
February 3, 2025
Journal
Journal of Cell Biology
Publisher
Rockefeller University Press
Citation
Kuan-Chung Su, Elena Radul, Nolan K. Maier, Mary-Jane Tsang, Claire Goul, Brittania Moodie, Océane Marescal, Heather R. Keys, Iain M. Cheeseman; Functional genetics reveals modulators of antimicrotubule drug sensitivity. J Cell Biol 3 February 2025; 224 (2): e202403065.
Version
Final published version
Abstract
Microtubules play essential roles in diverse cellular processes and are important pharmacological targets for treating human disease. Here, we sought to identify cellular factors that modulate the sensitivity of cells to antimicrotubule drugs. We conducted a genome-wide CRISPR/Cas9-based functional genetics screen in human cells treated with the microtubule-destabilizing drug nocodazole or the microtubule-stabilizing drug paclitaxel. We further conducted a focused secondary screen to test drug sensitivity for ∼1,400 gene targets across two distinct human cell lines and to additionally test sensitivity to the KIF11 inhibitor, STLC. These screens defined gene targets whose loss enhances or suppresses sensitivity to antimicrotubule drugs. In addition to gene targets whose loss sensitized cells to multiple compounds, we observed cases of differential sensitivity to specific compounds and differing requirements between cell lines. Our downstream molecular analysis further revealed additional roles for established microtubule-associated proteins and identified new players in microtubule function.
MIT Department
Whitehead Institute for Biomedical Research
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-Noncommercial-ShareAlike
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DOI of Published Version
https://doi.org/10.1083/jcb.202403065
