Regulation of Hematopoietic Stem Cell Differentiation by a Single Ubiquitin Ligase-substrate Complex

Overview

Journal Nat Immunol

Date 2010 Jan 19

PMID 20081848

Citations 72

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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