Loss of the proteasomal deubiquitinase USP14 induces growth defects and a senescence phenotype in colorectal cancer cells-Reference-Cited by-同舟云学术

Loss of the proteasomal deubiquitinase USP14 induces growth defects and a senescence phenotype in colorectal cancer cells

Published:2024-06-06 Issue:1 Volume:14 Page:
ISSN:2045-2322
Container-title:Scientific Reports
language:en
Short-container-title:Sci Rep

Author:

Gubat Johannes,Sjöstrand Linda,Selvaraju Karthik,Telli Kübra,D’Arcy Pádraig

Abstract

AbstractThe proteasome-associated deubiquitinase USP14 is a potential drug target. Using an inducible USP14 knockout system in colon cancer cells, we found that USP14 depletion impedes cellular proliferation, induces cell cycle arrest, and leads to a senescence-like phenotype. Transcriptomic analysis revealed altered gene expression related to cell division and cellular differentiation. USP14 knockout cells also exhibited changes in morphology, actin distribution, and expression of actin cytoskeletal components. Increased ubiquitin turnover was observed, offset by upregulation of polyubiquitin genes UBB and UBC. Pharmacological inhibition of USP14 with IU1 increased ubiquitin turnover but did not affect cellular growth or morphology. BioGRID data identified USP14 interactors linked to actin cytoskeleton remodeling, DNA damage repair, mRNA splicing, and translation. In conclusion, USP14 loss in colon cancer cells induces a transient quiescent cancer phenotype not replicated by pharmacologic inhibition of its deubiquitinating activity.

Funder

Cancerfonden

LiU Cancer

Linköping University

Publisher

Springer Science and Business Media LLC

Link

https://www.nature.com/articles/s41598-024-63791-5.pdf

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