| Project/Area Number |
09670148
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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 |
Pathological medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
FUKAMI Kiyoko Institute of Medical Science, The university of Tokyo,, 医科学研究所, 助手 (40181242)
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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 |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | phospholipase Cdelta4 / phosphatidylinositol turnover in nuclei / PIP2-binding protein / cell growth / PtdIns(4,5)P2 / イノシトールリン脂質代謝系 / PLCδ4 / 核内カルシウム / PHdomain |
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| Research Abstract |
1.Regulation of gene transcription by polyphosphoinositides.
We have first screened new phosphatidylinositol 4,5-bisphosphate (PIP2)-binding proteins by using anti-PIP2 antibody. PIP2-western blot revealed that histones as PIP2-binding proteins.
Histones are konwn to inhibit gene transcription. Then we examined the effect of phospholipids such as PIP2, PIP, PI, PC etc.on the transcriptional inhibition by histone Hl. PIP2 was found to antagonize the inhibition, remarkably. On the other hand, PC or PS didn't affect at all.
2.A novel phospholipase Cdelta4 (PLCdelta4) appears in nuclei in correlation to mitogenic signal.
Expression of PLCdelta4 was remarkably induced in Swiss 3T3 cells by treatment of serum. Examination of the diffence of expression in various cells revealed that PLCdelta4 protein exists much in oncogenic cells such as rat hepatoma AH7974 cells and C6 rat glioma cells.
3.Analysis of promoter region of mouse PLCdelta4 gene.
We have isolated mouse PLCdelta4 gene and analized promoter region of mouse PLCdelta4 gene. We found splicing isoforms which were found to regulate delta type of PLC negatively. Next we determined the 120 bp as minimam essential region for the transcription. Using this region, we examined the induction mechanism by measuringluciferase activity and gel shift assay. We found lysophosphatidic acid or bradykinin induded the transcription of PLCdelta4.
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