title: Cul4A is required for hematopoietic stem-cell engraftment and self-renewal.
abstract: 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.
authors.affiliation: Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Binghui
authors.initials: B
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Jia
authors.forename: David L
authors.initials: DL
authors.lastname: Waning
authors.forename: Feng-Chun
authors.initials: FC
authors.lastname: Yang
authors.forename: Laura S
authors.initials: LS
authors.lastname: Haneline
authors.forename: Kristin T
authors.initials: KT
authors.lastname: Chun
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D046528:Chimerism; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: C491940:Cul4a protein, mouse; D044842:Cullin Proteins