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Cited by 115Hematopoietic Stem Cell TransplantationRNA and protein synthesis mechanismsPI3K/AKT/mTOR signaling in cancer

The rate of protein synthesis in hematopoietic stem cells is limited partly by 4E-BPs

Open access
Signer, Robert A.J., Qi, Le, Zhao, Zhiyu, Thompson, David, Sigova, Alla A., Fan, Zi Peng, DeMartino, George N., Young, Richard A. +2 more·2016·Genes & Development
DOI 10.1101/gad.282756.116PMC PMC5002975
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Abstract

Adult stem cells must limit their rate of protein synthesis, but the underlying mechanisms remain largely unexplored. Differences in protein synthesis among hematopoietic stem cells (HSCs) and progenitor cells did not correlate with differences in proteasome activity, total RNA content, mRNA content, or cell division rate. However, adult HSCs had more hypophosphorylated eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and 4E-BP2 as compared with most other hematopoietic progenitors. Deficiency for 4E-BP1 and 4E-BP2 significantly increased global protein synthesis in HSCs, but not in other hematopoietic progenitors, and impaired their reconstituting activity, identifying a mechanism that promotes HSC maintenance by attenuating protein synthesis.

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  • Dual deletion of 4E-BP1/2 leads to increased protein synthesis, aberrant cell cycle activity, and HSC expansion.

    “dual deletion of 4E-BP1/2, which negatively regulates translation by inhibiting eIF4E, leads to increased protein synthesis, aberrant cell cycle activity, and HSC expansion (Signer et al., 2016).”

    From PU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress (2021) · cites this paper as Signer et al., 2016

    The Results and Discussion report increased protein synthesis and a modest increase in bone-marrow HSC frequency after dual 4E-BP1/2 deletion. They do not support aberrant cell-cycle activity: the increased HSC frequency was not associated with a significant change in the frequency of dividing HSCs. Page numbers were not available in our copy. (LLM, conf=0.90)

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Authors
Signer, R. A. J., Qi, L., Zhao, Z., Thompson, D., Sigova, A. A., Fan, Z. P., DeMartino, G. N., Young, R. A., Sonenberg, N., & Morrison, S. J.
Affiliations
  • Howard Hughes Medical Institute (US)
  • The University of Texas Southwestern Medical Center (US)
  • Whitehead Institute for Biomedical Research (US)
  • McGill University (CA)
ORCID
Venue
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Published
2016-08-01
Volume
30
Issue
15
Pages
1698-1703
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
DOI
10.1101/gad.282756.116
PMC
PMC5002975
OpenAlex
W2491651701
Cited by
115
References
5
Citations by year
2026: 7 · 2025: 18 · 2024: 12 · 2023: 17 · 2022: 12 · 2021: 14 · 2020: 10 · 2019: 10 · 2018: 9 · 2017: 4 · 2016: 1
Type
posted content
Language
en
Open access
Licence
cc-by
Locations
  • Genes & Development (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
  • eScholarship@McGill (McGill) (submittedVersion, cc-by-nc)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK100848)
  • Cancer Prevention and Research Institute of Texas
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
hematopoietic stem cells, protein synthesis, 4E-BP1, 4E-BP2, eIF4E-binding protein, hypophosphorylation, hematopoietic progenitor cells, stem cell maintenance, translational regulation
MeSH terms
Animals, Carrier Proteins, Cell Differentiation, Female, Hematopoietic Stem Cells, Male, Mice, Inbred C57BL, Phosphoproteins, Phosphorylation, Protein Biosynthesis, Sequence Deletion, Cell Cycle Proteins, Eukaryotic Initiation Factors, Proteasome Endopeptidase Complex, Adaptor Proteins, Signal Transducing, Mice

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