The mouse polyubiquitin gene UbC is essential for fetal liver development, cell‐cycle progression and stress tolerance
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UbC is one of two stress-inducible polyubiquitin genes in mammals and is thought to supplement the constitutive UbA genes in maintaining cellular ubiquitin (Ub) levels during episodes of cellular stress. We have generated mice harboring a targeted disruption of the UbC gene. UbC(-/-) embryos die between embryonic days 12.5 and 14.5 in utero, most likely owing to a severe defect in liver cell proliferation. Mouse embryonic fibroblasts from UbC(-/-) embryos exhibit reduced growth rates, premature senescence, increased apoptosis and delayed cell-cycle progression, with slightly, but significantly, decreased steady-state Ub levels. UbC(-/-) fibroblasts are hypersensitive to proteasome inhibitors and heat shock, and unable to adequately increase Ub levels in response to these cellular stresses. Most, but not all of the UbC(-/-) phenotypes can be rescued by providing additional Ub from a poly hemagglutinin-tagged Ub minigene expressed from the Hprt locus. We propose that UbC is regulated by a process that senses Ub pool dynamics. These data establish that UbC constitutes an essential source of Ub during cell proliferation and stress that cannot be compensated by other Ub genes.
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Three genes overlapped between the microglial and astrocyte factors that were not part of consensus mouse gene lists (UBC, DDIT4 and HSPB1), and these are part of cellular stress and damage response machinery.
“Finally, there were three genes that overlapped between the microglial and astrocyte factors that were not a part of consensus mouse gene lists (UBC, DDIT4 and HSPB1), but which unsurprisingly are also part of cellular stress and damage response machinery52–55.”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [54]
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- Authors
- Ryu, K., Maehr, R., Gilchrist, C. A., Long, M. A., Bouley, D. M., Mueller, B., Ploegh, H. L., & Kopito, R. R.
- Affiliations
- Stanford University (US)
- Harvard University (US)
- University of Auckland (NZ)
- University of British Columbia (CA)
- Stanford Medicine (US)
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Kopito, Ron R
- Venue
- The EMBO Journal
- Published
- 2007-05-10
- Volume
- 26
- Issue
- 11
- Pages
- 2693-2706
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1888680
- OpenAlex
- W2103805605
- Cited by
- 156
- References
- 39
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 9 · 2023: 3 · 2022: 10 · 2021: 8 · 2020: 6 · 2019: 7 · 2018: 20 · 2017: 16 · 2016: 2 · 2015: 10 · 2014: 14 · 2013: 12 · 2012: 7
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ResearchSpace (University of Auckland) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- fetal liver development, liver cell proliferation, cell cycle progression, premature senescence, apoptosis, proteasome inhibitors, heat shock, stress tolerance, embryonic lethality, hprt locus, mouse embryonic fibroblasts
- MeSH terms
- Animals, Cell Cycle, Fibroblasts, Gene Expression Regulation, Liver, Cellular Senescence, Mice, Knockout, Genes, Essential, Ubiquitin C, Fetal Development, Cell Proliferation, Mice
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