| First Author | Li B | Year | 2007 |
| Journal | Blood | Volume | 110 |
| Issue | 7 | Pages | 2704-7 |
| PubMed ID | 17616641 | Mgi Jnum | J:147012 |
| Mgi Id | MGI:3839083 | Doi | 10.1182/blood-2006-12-064154 |
| Citation | Li B, et al. (2007) Cul4A is required for hematopoietic stem-cell engraftment and self-renewal. Blood 110(7):2704-7 |
| abstractText | Several hematopoietic stem-cell (HSC) regulators are controlled by ubiquitin-mediated proteolysis, so the ubiquitin pathway might modulate HSC function. However, this hypothesis has not been formally tested. Cul4A encodes a core subunit of one ubiquitin ligase. Whereas Cul4A-deficient embryos die in utero, Cul4A-haploinsufficient mice are viable but exhibit abnormal hematopoiesis (fewer erythroid and primitive myeloid progenitors). Given these data, we examined whether Cul4A(+/-) HSCs might also be impaired. Using bone marrow transplantation assays, we determined that Cul4A(+/-) HSCs exhibit defects in engraftment and self-renewal capacity. These studies are the first to demonstrate that ubiquitin-mediated protein degradation is important for HSC function. Further, they indicate that a Cul4A ubiquitin ligase targets for degradation one or multiple HSC regulators. |
