| Project/Area Number |
09671431
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
TAKESHIMA Hideo Kumamoto Univ.Sch.Med., Instructor, 医学部, 助手 (70244134)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Yoshiki Kumamoto Univ.Sch.Med., Instructor, 医学部, 助手 (50304994)
NISHI Toru Kumamoto Univ.Hosp.Instructor, 医学部・附属病院, 助手 (00264309)
KOCHI Masato Kumamoto Univ.Sch.Med., Associate professor, 医学部, 助教授 (70178218)
USHIO Yukitaka Kumamoto Univ.Sch.Med., Professor, 医学部, 教授 (20028583)
KURATSU Jun-ichi Kagoshima Univ.Sch.Med., Professor (20145296)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | MCP-1 / monocyte / CCR2 / Oct-1 / C / EBP / promoter / gene regulation / glioma / グリオーマ / 単球 / ケモカイン / 受容体 / プロモーター / マクロファージ |
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| Research Abstract |
The human monocyte chemoattractant protein-1 receptor designated hCCR2 is an essential co-receptor in cell entry by the human immunodeficiency virus as well as a receptor for monocyte chemoattractant protein-1, a member of the family of C-C chemokines that mediate monocyte chemotaxis. To elucidate the molecular mechanisms underlying the transcriptional regulation of hCCR2, we cloned and sequenced the hCCR2 gene ; it was approximately 8 kb in length and consisted of three exons divided by two introns. In the 5'-flanking region, there were the typical mammalian promoter consensus elements, a CAAT box and a TATA box, resulting in a single transcription initiation site. In addition, we found clustered tissue-specific cis-regulatory elements such as GATA consensus sequences, Oct-1 binding sequences, and CAAT/enhancer-binding protein binding sequences. Luciferase assays with various promoter deletions and gel mobility shift assays indicated that three cis-regulatory elements located within the region from -89 to +118 are required for basal activity in THP-1 cells. One element is an octamer sequence 36-bp upstream from the TATA box ; it binds mainly to Oct-1 and is capable of increasing transcriptional activity. The other two elements, which are tandem recognition sites of the CAAT/enhancer-binding protein family, are located in the 5'-untranslated region and account for the transcriptional activation as well as the tissue specificity of hCCR2.
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