Cul4A is required for hematopoietic stem-cell engraftment and self-renewal

Binghui Li, Nan Jia, David L. Waning, Feng Chun Yang, Laura S. Haneline, Kristin T. Chun

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2704-2707
Number of pages4
JournalBlood
Volume110
Issue number7
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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