| Project/Area Number |
07044213
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Biological pharmacy
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| Research Institution | Hokkaido University |
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Principal Investigator |
ARIGA Sanae HOKKAIDO UNIVERSITY,COLLEGE OF MEDICAL TECHNOLOGY,PROFESSOR, 医療技術短期大学部, 教授 (90184283)
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| Co-Investigator(Kenkyū-buntansha) |
KITAURA Hirotake HOKKAIDO UNIVERSITY,FACULTY OF PHARMACEUTICAL SCIENCES,ASSISTANT PROFESSOR, 薬学部, 助手 (10281817)
ARIGA Hiroyoshi HOKKAIDO UNIVERSITY,FACULTY OF PHARMACEUTICAL SCIENCES,PROFESSOR, 薬学部, 教授 (20143505)
GALLI Ivo BERN UNIVERSITY HOSPITAL,DEPARTMENT OF INTERNAL MEDICINE,SENIOR SCIENTIST, 研究員
WANG Teresa スタンフォード大学, 医学センター, 教授
WANG Teresa S.-F. STANFORD UNIVERSITY,MEDICAL CENTER,PROFESSOR
根岸 文子 (財), 佐々木研究所, 研究員 (40177902)
IVO Galli ベルン大学病院, 研究員
TERESA S.ーF. スタンフォード大学, 医学センター, 教授
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1996: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | REPLICATION / TRANSCRIPTION / MSSP / C-MYC / CELL CYCLE / YEAST / DNA BINDING PROTEINS / AMY-1 / DNAポリメラーゼ / DNAポリメラーゼα / 核移行阻止 |
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| Research Abstract |
MSSP,myc single strand binding proteins, have been identified as replication/transcription factors and shown to form specific complex with various proteins including C-MYC and cdc kinase. In addition, MSSP directly bound to DNA polymerase alpha, which is a major enzyme of DNA replication, and stimulated its activity in vitro. Competitive binding to MSSP was observed among C-MYC,cdc kinase and DNA polymerase alpha. MSSP was thus suggested to play an important role in the 'licencing' process at the progression from the G1 phase to the S phase of the cell cycle. The analyzes of the genomic MSSP gene revealed that the expression of MSSP was regulated according to the cell cycle by the sequences upstreem from the promoter and the expression was induced in the early G1 phase and reached a peak from the late G1 to the early S phase as that of C-MYC.Since the introduction of MSSP to cells resulted in activation not only of replication but also of transcription from various promoters, MSSP was suggested to be regulatory factors for both replication and transcription. The results we have obtained, however, indicate that MSSP is directly involved in the regulation of replication initiation and make cells 'licensed' to enter the S phase together with C-MYC,and that the transcription is subsequently activated or repressed. Another C-MYC binding protein, AMY-1 (associated with C-MYC) , has been cloned by the yeast two-hybrid system. AMY-1, as well as MSSP,specifically recognizes the N-terminal region covering the myc boxes. AMY-1 has a transactivation activity and localizes on and along the nuclear membrane on the cytoplasmic side, but translocates into nucleus in the late G1 and the early S phase when the C-MYC expression becomes high. These results hence strongly suggest that the competitive binding to C-MYC between the replication factor MSSP and the transcription factor AMY-1 functions as a switch of the cell 'licencing' to the S phase by C-MYC.
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