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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / metabolism
  • Carrier Proteins / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Down-Regulation
  • Gene Deletion
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Leukemia, Myeloid, Acute / metabolism
  • Mice, Inbred C57BL
  • Polycomb Repressive Complex 1 / metabolism*
  • Polycomb-Group Proteins / metabolism
  • Protein Binding
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Small Interfering / metabolism
  • Ubiquitin-Protein Ligases / metabolism


  • BMI1 protein, human
  • Bmi1 protein, mouse
  • Carrier Proteins
  • Cyclin-Dependent Kinase Inhibitor p16
  • Polycomb-Group Proteins
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Ubap2L protein, human
  • Ubap2L protein, mouse
  • Polycomb Repressive Complex 1
  • Rnf2 protein, mouse
  • Ubiquitin-Protein Ligases