Regulation of hematopoietic stem cell differentiation by a single ubiquitin ligase-substrate complex Academic Article uri icon

Overview

MeSH Major

  • Cell Differentiation
  • Hematopoietic Stem Cells
  • Ubiquitin-Protein Ligases

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.

publication date

  • March 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2825759

Digital Object Identifier (DOI)

  • 10.1038/ni.1839

PubMed ID

  • 20081848

Additional Document Info

start page

  • 207

end page

  • 15

volume

  • 11

number

  • 3