title: UBAP2L is a novel BMI1-interacting protein essential for hematopoietic stem cell activity.
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.
authors.affiliation: Institute for Research in Immunology and Cancer and.
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Bordeleau
authors.affiliation: Institute for Research in Immunology and Cancer and.
authors.forename: Romain
authors.initials: R
authors.lastname: Aucagne
authors.affiliation: Institute for Research in Immunology and Cancer and.
authors.forename: Jalila
authors.initials: J
authors.lastname: Chagraoui
authors.affiliation: Institute for Research in Immunology and Cancer and.
authors.forename: Simon
authors.initials: S
authors.lastname: Girard
authors.affiliation: Institute for Research in Immunology and Cancer and.
authors.forename: Nadine
authors.initials: N
authors.lastname: Mayotte
authors.affiliation: Institute for Research in Immunology and Cancer and.
authors.forename: Eric
authors.initials: E
authors.lastname: Bonneil
authors.affiliation: Institute for Research in Immunology and Cancer and Departments of Biochemistry and Chemistry, Université de Montréal, Montréal, QC, Canada;
authors.forename: Pierre
authors.initials: P
authors.lastname: Thibault
authors.affiliation: Institute for Research in Immunology and Cancer and.
authors.forename: Caroline
authors.initials: C
authors.lastname: Pabst
authors.affiliation: 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;
authors.forename: Anne
authors.initials: A
authors.lastname: Bergeron
authors.affiliation: 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;
authors.forename: Frédéric
authors.initials: F
authors.lastname: Barabé
authors.affiliation: Division of Hematology and Leukemia Cell Bank of Quebec, Maisonneuve-Rosemont Hospital, Montréal, QC, Canada; and.
authors.forename: Josée
authors.initials: J
authors.lastname: Hébert
authors.affiliation: Institute for Research in Immunology and Cancer and.
authors.forename: Martin
authors.initials: M
authors.lastname: Sauvageau
authors.affiliation: Institute for Research in Immunology and Cancer and.
authors.forename: Christel
authors.initials: C
authors.lastname: Boutonnet
authors.affiliation: Institute for Research in Immunology and Cancer and Department of Pharmacology and.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Meloche
authors.affiliation: 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.
authors.forename: Guy
authors.initials: G
authors.lastname: Sauvageau
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D015536:Down-Regulation; D017353:Gene Deletion; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D008810:Mice, Inbred C57BL; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D063146:Polycomb-Group Proteins / Q000378:metabolism; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: C069077:BMI1 protein, human; C489421:Bmi1 protein, mouse; D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; C000595671:Ubap2L protein, human; C000595670:Ubap2L protein, mouse; D063150:Polycomb Repressive Complex 1; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases