| First Author | Reavie L | Year | 2010 |
| Journal | Nat Immunol | Volume | 11 |
| Issue | 3 | Pages | 207-15 |
| PubMed ID | 20081848 | Mgi Jnum | J:158371 |
| Mgi Id | MGI:4438663 | Doi | 10.1038/ni.1839 |
| Citation | Reavie L, et al. (2010) Regulation of hematopoietic stem cell differentiation by a single ubiquitin ligase-substrate complex. Nat Immunol 11(3):207-15 |
| abstractText | 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. |
