title: The rate of protein synthesis in hematopoietic stem cells is limited partly by 4E-BPs.
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.
authors: Howard Hughes Medical Institute, Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; Division of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA;
authors: Robert A J
authors: RA
authors: Signer
authors: Howard Hughes Medical Institute, Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
authors: Le
authors: L
authors: Qi
authors: Howard Hughes Medical Institute, Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
authors: Zhiyu
authors: Z
authors: Zhao
authors: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
authors: David
authors: D
authors: Thompson
authors: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA;
authors: Alla A
authors: AA
authors: Sigova
authors: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA;
authors: Zi Peng
authors: ZP
authors: Fan
authors: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
authors: George N
authors: GN
authors: DeMartino
authors: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
authors: Richard A
authors: RA
authors: Young
authors: Department of Biochemistry, Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.
authors: Nahum
authors: N
authors: Sonenberg
authors: Howard Hughes Medical Institute, Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
authors: Sean J
authors: SJ
authors: Morrison
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000235:genetics; D039642:Eukaryotic Initiation Factors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; C491255:Eif4ebp2 protein, mouse; D039642:Eukaryotic Initiation Factors; D010750:Phosphoproteins; D046988:Proteasome Endopeptidase Complex
keywords: 4E-BP; protein synthesis; stem cell