The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Increased proteasome activity in human embryonic stem cells is regulated by PSMD11
Open accessAbstract
Embryonic stem cells can replicate continuously in the absence of senescence and, therefore, are immortal in culture. Although genome stability is essential for the survival of stem cells, proteome stability may have an equally important role in stem-cell identity and function. Furthermore, with the asymmetric divisions invoked by stem cells, the passage of damaged proteins to daughter cells could potentially destroy the resulting lineage of cells. Therefore, a firm understanding of how stem cells maintain their proteome is of central importance. Here we show that human embryonic stem cells (hESCs) exhibit high proteasome activity that is correlated with increased levels of the 19S proteasome subunit PSMD11 (known as RPN-6 in Caenorhabditis elegans) and a corresponding increased assembly of the 26S/30S proteasome. Ectopic expression of PSMD11 is sufficient to increase proteasome assembly and activity. FOXO4, an insulin/insulin-like growth factor-I (IGF-I) responsive transcription factor associated with long lifespan in invertebrates, regulates proteasome activity by modulating the expression of PSMD11 in hESCs. Proteasome inhibition in hESCs affects the expression of pluripotency markers and the levels of specific markers of the distinct germ layers. Our results suggest a new regulation of proteostasis in hESCs that links longevity and stress resistance in invertebrates to hESC function and identity.
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“this observation suggests that iPSCs and germ layer cells may compensate for the detrimental effects of PSMC5 variant p.(Arg325Trp) by monoallelic expression of the wild-type PSMC5 allele and/or an enhanced capacity to selectively eliminate defective proteasome assembly intermediates27.”
From Investigating the neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies (2025) · cites this paper as [26]
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“FOXO4 promotes proteasome activity in hESCs by regulating PSDM11 expression, thereby encouraging proteostasis and maintenance of pluripotency markers, such as POU5F1, OCT4, NANOG, SOX2, UTF1, DPPA4, DPPA2, ZFP42 and TERT81.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [81]
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Metadata
- Authors
- Vilchez, D., Boyer, L., Morantte, I., Lutz, M., Merkwirth, C., Joyce, D., Spencer, B., Page, L., Masliah, E., Berggren, W. T., Gage, F. H., & Dillin, A.
- Affiliations
- Salk Institute for Biological Studies (US)
- University of California San Diego (US)
- Scripps Research Institute (US)
- Corresponding author
- Dillin, Andrew
- ORCID
- Venue
- Nature
- Published
- 2012-09
- Volume
- 489
- Issue
- 7415
- Pages
- 304-308
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5215918
- OpenAlex
- W2089761608
- Cited by
- 388
- References
- 26
- Citations by year
- 2026: 7 · 2025: 25 · 2024: 24 · 2023: 17 · 2022: 24 · 2021: 42 · 2020: 39 · 2019: 35 · 2018: 36 · 2017: 30 · 2016: 24 · 2015: 31 · 2014: 30 · 2013: 19 · 2012: 5
- FWCI
- 10.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (R37AG018440, P01AG031097)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- proteasome activity, 19S proteasome, FOXO4, DAF-16, human embryonic stem cells, stem cell differentiation, proteostasis, Caenorhabditis elegans, glucagon-like peptide-1, lifespan extension, proteotoxic stress, genome stability, aging, insulin/IGF-1 signaling
- MeSH terms
- Cell Differentiation, Cell Line, Humans, Transcription Factors, Up-Regulation, Cell Cycle Proteins, Protein Subunits, Pluripotent Stem Cells, Proteasome Endopeptidase Complex, Forkhead Transcription Factors, Embryonic Stem Cells, HEK293 Cells, Proteasome Inhibitors
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