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Blood. 2014 Oct 9;124(15):2362-9. doi: 10.1182/blood-2014-01-548651. Epub 2014 Sep 2.

UBAP2L is a novel BMI1-interacting protein essential for hematopoietic stem cell activity.

Author information

1
Institute for Research in Immunology and Cancer and.
2
Institute for Research in Immunology and Cancer and Departments of Biochemistry and Chemistry, Université de Montréal, Montréal, QC, Canada;
3
Centre Hospitalier Universitaire de Québec, Centre de Recherche du Centre Hospitalier de l'Université Laval and Hôpital de l'Enfant-Jésus, Quebec City, QC, Canada;
4
Centre Hospitalier Universitaire de Québec, Centre de Recherche du Centre Hospitalier de l'Université Laval and Hôpital de l'Enfant-Jésus, Quebec City, QC, Canada; Department of Medicine, Université Laval, Quebec City, QC, Canada;
5
Division of Hematology and Leukemia Cell Bank of Quebec, Maisonneuve-Rosemont Hospital, Montréal, QC, Canada; and.
6
Institute for Research in Immunology and Cancer and Department of Pharmacology and.
7
Institute for Research in Immunology and Cancer and Division of Hematology and Leukemia Cell Bank of Quebec, Maisonneuve-Rosemont Hospital, Montréal, QC, Canada; and Department of Medicine, Université de Montréal, Montréal, QC, Canada.

Abstract

Multipotent long-term repopulating hematopoietic stem cells (LT-HSCs) can self-renew or differentiate into the less primitive short-term repopulating stem cells (ST-HSCs), which themselves produce progenitors that ensure the daily supply of all essential blood components. The Polycomb group (PcG) protein BMI1 is essential for the activity of both HSCs and progenitor cells. Although BMI1 operates by suppressing the Ink4a/Arf locus in progenitors and ST-HSCs, the mechanisms through which this gene regulates the activity of LT-HSCs remain poorly understood. Toward this goal, we isolated BMI1-containing protein complexes and identified UBAP2L as a novel BMI1-interacting protein. We also showed that UBAP2L is preferentially expressed in mouse and human HSC-enriched populations when compared with more mature cell types, and that this gene is essential for the activity of LT-HSCs. In contrast to what is observed for Bmi1 knockdown, we found that UBAP2L depletion does not affect the Ink4a/Arf locus. Given that we demonstrated that BMI1 overexpression is able to rescue the deleterious effects of Ubap2l downregulation on LT-HSC activity and that UBAP2L is part of a PcG subcomplex comprising BMI1, we propose a model in which at least 2 different BMI1-containing PcG complexes regulate HSC activity, which are distinguishable by the presence of UBAP2L.

PMID:
25185265
PMCID:
PMC4192749
DOI:
10.1182/blood-2014-01-548651
[Indexed for MEDLINE]
Free PMC Article

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