Regulation of hematopoietic stem cell differentiation by a single ubiquitin ligase-substrate complex

Academic Article

Abstract

  • Hematopoietic stem cell (HSC) differentiation is regulated by cell-intrinsic and cell-extrinsic cues. In addition to transcriptional regulation, post-translational regulation may also control HSC differentiation. To test this hypothesis, we visualized the ubiquitin-regulated protein stability of a single transcription factor, c-Myc. The stability of c-Myc protein was indicative of HSC quiescence, and c-Myc protein abundance was controlled by the ubiquitin ligase Fbw7. Fine changes in the stability of c-Myc protein regulated the HSC gene-expression signature. Using whole-genome genomic approaches, we identified specific regulators of HSC function directly controlled by c-Myc binding; however, adult HSCs and embryonic stem cells sensed and interpreted c-Myc-regulated gene expression in distinct ways. Our studies show that a ubiquitin ligase-substrate pair can orchestrate the molecular program of HSC differentiation. © 2010 Nature America, Inc. All rights reserved.
  • Authors

    Published In

  • Nature Immunology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Reavie L; Gatta GD; Crusio K; Aranda-Orgilles B; Buckley SM; Thompson B; Lee E; Gao J; Bredemeyer AL; Helmink BA
  • Start Page

  • 207
  • End Page

  • 215
  • Volume

  • 11
  • Issue

  • 3