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

Linsey Reavie, Giusy Della Gatta, Kelly Crusio, Beatriz Aranda-Orgilles, Shannon M. Buckley, Benjamin Thompson, Eugine Lee, Jie Gao, Andrea L. Bredemeyer, Beth A. Helmink, Jiri Zavadil, Barry P. Sleckman, Teresa Palomero, Adolfo Ferrando, Iannis Aifantis

Research output: Contribution to journalArticle

70 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)207-215
Number of pages9
JournalNature Immunology
Volume11
Issue number3
DOIs
StatePublished - Mar 1 2010

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Ligases
Hematopoietic Stem Cells
Ubiquitin
Cell Differentiation
Proto-Oncogene Proteins c-myc
myc Genes
Adult Stem Cells
Protein Stability
Embryonic Stem Cells
Transcriptome
Cues
Transcription Factors
Genome
Gene Expression

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Reavie, L., Gatta, G. D., Crusio, K., Aranda-Orgilles, B., Buckley, S. M., Thompson, B., ... Aifantis, I. (2010). Regulation of hematopoietic stem cell differentiation by a single ubiquitin ligase-substrate complex. Nature Immunology, 11(3), 207-215. https://doi.org/10.1038/ni.1839

Regulation of hematopoietic stem cell differentiation by a single ubiquitin ligase-substrate complex. / Reavie, Linsey; Gatta, Giusy Della; Crusio, Kelly; Aranda-Orgilles, Beatriz; Buckley, Shannon M.; Thompson, Benjamin; Lee, Eugine; Gao, Jie; Bredemeyer, Andrea L.; Helmink, Beth A.; Zavadil, Jiri; Sleckman, Barry P.; Palomero, Teresa; Ferrando, Adolfo; Aifantis, Iannis.

In: Nature Immunology, Vol. 11, No. 3, 01.03.2010, p. 207-215.

Research output: Contribution to journalArticle

Reavie, L, Gatta, GD, Crusio, K, Aranda-Orgilles, B, Buckley, SM, Thompson, B, Lee, E, Gao, J, Bredemeyer, AL, Helmink, BA, Zavadil, J, Sleckman, BP, Palomero, T, Ferrando, A & Aifantis, I 2010, 'Regulation of hematopoietic stem cell differentiation by a single ubiquitin ligase-substrate complex', Nature Immunology, vol. 11, no. 3, pp. 207-215. https://doi.org/10.1038/ni.1839
Reavie, Linsey ; Gatta, Giusy Della ; Crusio, Kelly ; Aranda-Orgilles, Beatriz ; Buckley, Shannon M. ; Thompson, Benjamin ; Lee, Eugine ; Gao, Jie ; Bredemeyer, Andrea L. ; Helmink, Beth A. ; Zavadil, Jiri ; Sleckman, Barry P. ; Palomero, Teresa ; Ferrando, Adolfo ; Aifantis, Iannis. / Regulation of hematopoietic stem cell differentiation by a single ubiquitin ligase-substrate complex. In: Nature Immunology. 2010 ; Vol. 11, No. 3. pp. 207-215.
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