Identification of a novel transcriptional activator, BSAC, by a functional cloning to inhibit tumor necrosis factor-induced cell death

J Biol Chem. 2002 Aug 9;277(32):28853-60. doi: 10.1074/jbc.M203190200. Epub 2002 May 17.


Tumor necrosis factor (TNF) is a multifunctional cytokine, which induces proliferation or death in a cell type-dependent manner. We previously showed that murine embryonic fibroblasts (MEFs) from TNF receptor-associated factor 2 (Traf2) and Traf5 double-deficient (double knockout (DKO)) mice were highly susceptible to TNF-induced cell death. By functional cloning to rescue DKO MEFs from TNF-induced cell death, we have identified a novel gene, Bsac. BSAC is composed of N-terminal basic, SAP (SAF-A/B, Acinus, PIAS), and coiled-coil domains. BSAC is a nuclear protein, and overexpression of BSAC potently activates promoters containing A + T-rich sequences named CArG boxes. Domain mapping analysis revealed that both N-terminal basic and C-terminal proline-rich sequence are required for the transcriptional activity. Overexpression of BSAC in DKO MEFs partially inhibited TNF-induced cell death by suppressing activation of caspases. Interestingly, inhibition of TNF-induced cell death was not observed in DKO MEFs transfected with either N-terminal or C-terminal deletion mutant of BSAC, revealing an intimate correlation between transcriptional activity and antiapoptotic function. Recently, a human homologue of BSAC named MAL/MKL1 (megakaryocytic acute leukemia/megakaryoblastic leukemia-1) was identified as a fusion transcript generated by t(1,22) translocation in acute megakaryoblastic leukemia. Collectively, BSAC is a novel transcriptional activator with antiapoptotic function, which may be involved in the leukemogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Blotting, Northern
  • Cell Death
  • Cell Line
  • Cloning, Molecular
  • DNA-Binding Proteins
  • Dose-Response Relationship, Drug
  • Fibroblasts / metabolism
  • Gene Library
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Leukemia / metabolism
  • Mice
  • Models, Genetic
  • Molecular Sequence Data
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / chemistry*
  • Oncogene Proteins, Fusion
  • Plasmids / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Time Factors
  • Tissue Distribution
  • Trans-Activators / biosynthesis*
  • Trans-Activators / chemistry*
  • Transcription, Genetic*
  • Transcriptional Activation
  • Transfection
  • Tumor Necrosis Factor-alpha / metabolism*


  • DNA-Binding Proteins
  • MRTFA protein, human
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • Trans-Activators
  • Tumor Necrosis Factor-alpha

Associated data

  • GENBANK/AF385582