Loss of the tumor suppressor BAP1 causes myeloid transformation Academic Article uri icon

Overview

MeSH Major

  • Cell Transformation, Neoplastic
  • Genes, Tumor Suppressor
  • Leukemia, Myelomonocytic, Chronic
  • Myelodysplastic Syndromes
  • Tumor Suppressor Proteins
  • Ubiquitin Thiolesterase

abstract

  • De-ubiquitinating enzyme BAP1 is mutated in a hereditary cancer syndrome with increased risk of mesothelioma and uveal melanoma. Somatic BAP1 mutations occur in various malignancies. We show that mouse Bap1 gene deletion is lethal during embryogenesis, but systemic or hematopoietic-restricted deletion in adults recapitulates features of human myelodysplastic syndrome (MDS). Knockin mice expressing BAP1 with a 3xFlag tag revealed that BAP1 interacts with host cell factor-1 (HCF-1), O-linked N-acetylglucosamine transferase (OGT), and the polycomb group proteins ASXL1 and ASXL2 in vivo. OGT and HCF-1 levels were decreased by Bap1 deletion, indicating a critical role for BAP1 in stabilizing these epigenetic regulators. Human ASXL1 is mutated frequently in chronic myelomonocytic leukemia (CMML) so an ASXL/BAP1 complex may suppress CMML. A BAP1 catalytic mutation found in a MDS patient implies that BAP1 loss of function has similar consequences in mice and humans.

publication date

  • September 21, 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5201002

Digital Object Identifier (DOI)

  • 10.1126/science.1221711

PubMed ID

  • 22878500

Additional Document Info

start page

  • 1541

end page

  • 6

volume

  • 337

number

  • 6101