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 journalArticlepeer-review

95 Scopus citations


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
Pages (from-to)207-215
Number of pages9
JournalNature immunology
Issue number3
StatePublished - Mar 2010


Dive into the research topics of 'Regulation of hematopoietic stem cell differentiation by a single ubiquitin ligase-substrate complex'. Together they form a unique fingerprint.

Cite this