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Peer-reviewedCC BY 4.0PLOS One

The COP9 signalosome subunit CSN1 regulates glioblastoma stem cell growth

  • Samir Assaf1
  • Kyle Heemskerk2
  • Xiaoguang Hao3
  • H. Artee Luchman
  • Samuel Weiss
  1. 1Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  2. 2Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  3. 3Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada
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Abstract

The COP9 signalosome is composed of 8 subunits (CSN1-CSN8) and plays a key role in regulating the activity of the ubiquitin-proteasome system by modulating Cullin-RING ubiquitin ligases. While the function of the COP9 signalosome in regulating protein homeostasis is well established, little is known about its role in glioblastoma. Here, using patient-derived glioblastoma stem cell lines, we identified CSN1 as a crucial COP9 signalosome subunit for in vitro growth. CSN1 knockout was further found to significantly extend survival in orthotopic glioblastoma xenograft models. Transcriptomic analysis revealed that CSN1 knockout disrupted transcriptional programs involved in cell cycle progression and activated apoptotic pathways. Molecular analysis further determined that CSN1 is required for COP9 signalosome complex assembly and regulates AP-1 activation via JNK1/2/3 and c-Jun phosphorylation. These results highlight the essentiality of CSN1 for glioblastoma stem cell growth and provide insights into the cellular mechanisms controlled by CSN1 and the COP9 signalosome.

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Cite

BibTeXRIS
BibTeX
@article{assaf2026cop9,
  title = {{The COP9 signalosome subunit CSN1 regulates glioblastoma stem cell growth}},
  author = {Samir Assaf and Kyle Heemskerk and Xiaoguang Hao and H. Artee Luchman and Samuel Weiss},
  journal = {PLOS One},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pone.0358568},
  url = {https://doi.org/10.1371/journal.pone.0358568},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The COP9 signalosome subunit CSN1 regulates glioblastoma stem cell growth
AU  - Samir Assaf
AU  - Kyle Heemskerk
AU  - Xiaoguang Hao
AU  - H. Artee Luchman
AU  - Samuel Weiss
PY  - 2026
DA  - 2026/09/17
JO  - PLOS One
DO  - 10.1371/journal.pone.0358568
UR  - https://doi.org/10.1371/journal.pone.0358568
AB  - The COP9 signalosome is composed of 8 subunits (CSN1-CSN8) and plays a key role in regulating the activity of the ubiquitin-proteasome system by modulating Cullin-RING ubiquitin ligases. While the function of the COP9 signalosome in regulating protein homeostasis is well established, little is known about its role in glioblastoma. Here, using patient-derived glioblastoma stem cell lines, we identified CSN1 as a crucial COP9 signalosome subunit for in vitro growth. CSN1 knockout was further found to significantly extend survival in orthotopic glioblastoma xenograft models. Transcriptomic analysis revealed that CSN1 knockout disrupted transcriptional programs involved in cell cycle progression and activated apoptotic pathways. Molecular analysis further determined that CSN1 is required for COP9 signalosome complex assembly and regulates AP-1 activation via JNK1/2/3 and c-Jun phosphorylation. These results highlight the essentiality of CSN1 for glioblastoma stem cell growth and provide insights into the cellular mechanisms controlled by CSN1 and the COP9 signalosome.
SN  - 1932-6203
ER  -