New classification of infantile leukemia using lineage-specific transcription
| Project/Area Number |
06670759
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | HIROSAKI UNIVERSITY |
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Principal Investigator |
ITO Etsuro Hirosaki University School of Medicine, Department of Pediatrics, Assistant professor, 医学部附属病院, 講師 (20168339)
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| Co-Investigator(Kenkyū-buntansha) |
ARAI Koji Hirosaki University School of Medicine, Department of Pediatrics, Lecturer, 医学部, 助手 (40232011)
TOKI Tsutom Hirosaki University School of Medicine, Department of Pediatrics, Lecturer, 医学部, 助手 (50195731)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | MEGAKARYOCYTES / NF-E2 TRANSCRIPTION FACTOR / MAF FAMILY / 組織特異的転写因子 |
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| Research Abstract |
Transcription factor NF-E2, which is heterodimeric protein complex comprised of products of p45 and the small maf family protooncogene (p18), is crucial for regulation of erythroid-specific gene expression and platelet formation. To characterize human p18, we isolated human cDNAs encoding the small Maf family protein MafK and MafG.The mafK gene and mafG gene encode proteins consisting of 156 and 162 amino acid residues, respectively and the molecular weight of these proteins are approximately 18kDa. MafK and MafG contain a basic DNA binding domain and a leucin zipper and lack putative trans-activator domain. The deduced amino acie sequence of human MafK or MafG showed 93% identity with that of its putative counterpart in chicken. The bacterially expressed MafK and MafG proteins form heterodimers with p45, which can efficiently bind to the NF-E2 probe. The homodimers of small Maf proteins also bind to NF-E2 probe.
However, binding of p45/small Maf heterodimer to NF-E2 probe is more prominent than that of small Maf homodimers. In transient transfection assays, small Mafs activate transcription of NF-E2 site dependent reporter genes in the presence of p45, whereas small Mafs repress the transcription in the abscence of p45. mRNAs for MafK and MafG are detected in all human tissues examined to date. The level of mafK transcripts were relatively high in heart, skeletal muscle and placenta. The level of mafG transcripts were less variable among tissues. The mafK and mafG mRNAs are expressed in all hematopoietic cell lines including erythroid and megakaryocytic lineages and the blast cells from all cases with infantile leukemia. These results suggest that human small Mafs play important regulatory roles in hematopoietic cells as a partner of p45 NF-E2 or the other CNC family proteins.
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Report
(3 results)
Research Products
(4 results)
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[Publications] Ito, E., 1.Ito, E., Kasai, M., Hayashi, Y., Toki, T., Arai, K., Yokoyama, S., Kato, K., Tachibna, N., Yamamoto, M.and Yokoyama, M.: "Expression of erythroid-specific genes in acute megakaryoblastic leukaemia and transient myeloproliferative disorder in Down's syndrome" Brit.J.Haematol.90. 607-614 (1995)
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[Publications] Toki, T., Itoh, J., Arai, K., Kitazawa, J., Yokoyama, M., Igarashi, K., Yamamoto, M.and Ito, E.: "Abundant expression of erythroid transcription factor p45 NF-E2 mRNA in human peripheral granulocytes" Biochem.Biophys.Res.Commun.(in press).
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