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

Tomonari Sasazuki, Taisuke Sawada, Sachiko Sakon, Toshio Kitamura, Takuma Kishi, Tatsuma Okazaki, Mitsuo Katano, Masao Tanaka, Mamoru Watanabe, Hideo Yagita, K. Okumura, Hiroyasu Nakano

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)28853-28860
Number of pages8
JournalThe Journal of biological chemistry
Volume277
Issue number32
DOIs
Publication statusPublished - 2002 Aug 9
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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