The rate of protein synthesis in hematopoietic stem cells is limited partly by 4E-BPs
- Robert A.J. Signer1,2,
- Le Qi1,
- Zhiyu Zhao1,
- David Thompson3,
- Alla A. Sigova4,
- Zi Peng Fan4,
- George N. DeMartino3,
- Richard A. Young4,5,
- Nahum Sonenberg6 and
- Sean J. Morrison1
- 1Howard Hughes Medical Institute, Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
- 2Division of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA;
- 3Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
- 4Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA;
- 5Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
- 6Department of Biochemistry, Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada
- Corresponding authors: sean.morrison{at}utsouthwestern.edu, rsigner{at}ucsd.edu
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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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.282756.116.
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Freely available online through the Genes & Development Open Access option.
- Received April 16, 2016.
- Accepted July 18, 2016.
This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
