Fusion of OTT to BSAC results in aberrant up-regulation of transcriptional activity

J Biol Chem. 2008 Sep 26;283(39):26820-8. doi: 10.1074/jbc.M802315200. Epub 2008 Jul 30.


OTT/RBM15-BSAC/MAL/MKL1/MRTF-A was identified as a fusion transcript generated by t(1;22)(p13;q13) in acute megakaryoblastic leukemia. Previous studies have shown that BSAC (basic, SAP, and coiled-coil domain) activates the promoters containing CArG boxes via interaction with serum response factor, and OTT (one twenty-two) negatively regulates the development of megakaryocytes and myeloid cells. However, the mechanism by which OTT-BSAC promotes leukemia is largely unknown. Here we show that OTT-BSAC, but not BSAC or OTT strongly activates several promoters containing a transcription factor Yin Yang 1-binding sequence. In addition, although BSAC predominantly localizes in the cytoplasm and its nuclear translocation is considered to be regulated by the Rho-actin signaling pathway, OTT-BSAC exclusively localizes in the nucleus. Moreover, OTT interacts with histone deacetylase 3, but this interaction is abolished in OTT-BSAC. Collectively, these functional and spatial changes of OTT and BSAC caused by the fusion might perturb their functions, culminating in the development of acute megakaryoblastic leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Cell Line, Tumor
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Humans
  • Leukemia, Megakaryoblastic, Acute / genetics
  • Leukemia, Megakaryoblastic, Acute / metabolism*
  • Megakaryocytes / metabolism
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism*
  • Protein Structure, Tertiary / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Response Elements* / genetics
  • Trans-Activators
  • Transcription, Genetic* / genetics
  • Up-Regulation / genetics
  • YY1 Transcription Factor / genetics
  • YY1 Transcription Factor / metabolism


  • DNA-Binding Proteins
  • MRTFA protein, human
  • Oncogene Proteins, Fusion
  • RBM15 protein, human
  • RNA-Binding Proteins
  • Trans-Activators
  • YY1 Transcription Factor
  • YY1 protein, human
  • Histone Deacetylases
  • histone deacetylase 3