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

Robert A J Signer, Le Qi, Zhiyu Zhao, David Thompson, Alla A. Sigova, Zi Peng Fan, George N. Demartino, Richard A. Young, Nahum Sonenberg, Sean J. Morrison

Research output: Contribution to journalArticle

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1698-1703
Number of pages6
JournalGenes and Development
Volume30
Issue number15
DOIs
StatePublished - Aug 1 2016

Keywords

  • 4E-BP
  • Protein synthesis
  • Stem cell

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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