title: Identification of a novel transcriptional activator, BSAC, by a functional cloning to inhibit tumor necrosis factor-induced cell death.
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.
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Sasazuki
authors.forename: Taisuke
authors.initials: T
authors.lastname: Sawada
authors.forename: Sachiko
authors.initials: S
authors.lastname: Sakon
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitamura
authors.forename: Takuma
authors.initials: T
authors.lastname: Kishi
authors.forename: Tatsuma
authors.initials: T
authors.lastname: Okazaki
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Katano
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Nakano
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D016923:Cell Death; D002460:Cell Line; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D015723:Gene Library; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D015514:Oncogene Proteins, Fusion; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014018:Tissue Distribution; D015534:Trans-Activators / Q000096:biosynthesis* / Q000737:chemistry*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C431575:MRTFA protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha