Author:
Signer Robert A.J.,Qi Le,Zhao Zhiyu,Thompson David,Sigova Alla A.,Fan Zi Peng,DeMartino George N.,Young Richard A.,Sonenberg Nahum,Morrison Sean J.
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.
Funder
Howard Hughes Medical Institute
National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases
Cancer Prevention and Research Institute of Texas
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
82 articles.
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