PMID- 12019265 OWN - NLM STAT- MEDLINE DCOM- 20020909 LR - 20210206 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 277 IP - 32 DP - 2002 Aug 9 TI - Identification of a novel transcriptional activator, BSAC, by a functional cloning to inhibit tumor necrosis factor-induced cell death. PG - 28853-60 AB - 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. FAU - Sasazuki, Tomonari AU - Sasazuki T AD - Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. FAU - Sawada, Taisuke AU - Sawada T FAU - Sakon, Sachiko AU - Sakon S FAU - Kitamura, Toshio AU - Kitamura T FAU - Kishi, Takuma AU - Kishi T FAU - Okazaki, Tatsuma AU - Okazaki T FAU - Katano, Mitsuo AU - Katano M FAU - Tanaka, Masao AU - Tanaka M FAU - Watanabe, Mamoru AU - Watanabe M FAU - Yagita, Hideo AU - Yagita H FAU - Okumura, Ko AU - Okumura K FAU - Nakano, Hiroyasu AU - Nakano H LA - eng SI - GENBANK/AF385582 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20020517 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (DNA-Binding Proteins) RN - 0 (MRTFA protein, human) RN - 0 (Nuclear Proteins) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (Trans-Activators) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Amino Acid Sequence MH - Animals MH - Apoptosis MH - Blotting, Northern MH - Cell Death MH - Cell Line MH - Cloning, Molecular MH - DNA-Binding Proteins MH - Dose-Response Relationship, Drug MH - Fibroblasts/metabolism MH - Gene Library MH - Genes, Reporter MH - HeLa Cells MH - Humans MH - Leukemia/metabolism MH - Mice MH - Models, Genetic MH - Molecular Sequence Data MH - Nuclear Proteins/*biosynthesis/*chemistry MH - Oncogene Proteins, Fusion MH - Plasmids/metabolism MH - Protein Binding MH - Protein Structure, Tertiary MH - Sequence Homology, Amino Acid MH - Time Factors MH - Tissue Distribution MH - Trans-Activators/*biosynthesis/*chemistry MH - *Transcription, Genetic MH - Transcriptional Activation MH - Transfection MH - Tumor Necrosis Factor-alpha/*metabolism EDAT- 2002/05/23 10:00 MHDA- 2002/09/11 10:01 CRDT- 2002/05/23 10:00 PHST- 2002/05/23 10:00 [pubmed] PHST- 2002/09/11 10:01 [medline] PHST- 2002/05/23 10:00 [entrez] AID - S0021-9258(20)70290-5 [pii] AID - 10.1074/jbc.M203190200 [doi] PST - ppublish SO - J Biol Chem. 2002 Aug 9;277(32):28853-60. doi: 10.1074/jbc.M203190200. Epub 2002 May 17.