Details

Autor(en) / Beteiligte

• Reavie, Linsey
• Della Gatta, Giusy
• 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

Titel

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

Ist Teil von

• Nature immunology, 2010-03, Vol.11 (3), p.207-215

Ort / Verlag

United States

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.