| Project/Area Number |
11670152
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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 | University of Occupational and Environmental Health |
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Principal Investigator |
KOHNO Kimitoshi Univ.of Occup.&Envir.Health, School of Medicine, Professor, 医学部, 教授 (00153479)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | YB-1 / cisplatin / p53 / MDR1 / p21 / exonuclease / 卵巣癌 / 大腸癌 / 細胞増殖 / Topo II / PCNA |
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| Research Abstract |
The Y-box binding protein, YB-1, belongs to a family of multifunctional proteins which regulate gene expression on both transcriptional and translational levels. The tumor suppressor gene p53 displays growth suppressive properties by regulating gene expression through transcriptional regulation. We now demonstrate that YB-1 directly interacts with p53. Gel mobility shift assays showed that the interaction of YB-1 with p53 stimulated the sequence-specific DNA binding of p53 to its consensus sequence. By contrast, this interaction inhibited the binding of YB-1. These findings delineate a straightforward mechanism for gene expression through p53-YB-1 interaction. We have previously shown that Y box-binding protein-1 (YB-1) binds preferentially to cisplatin-modified Y box sequences. We found that the cold shock domain of the protein is necessary but not sufficient for double-stranded DNA binding while the C-tail domain interacts with both single-stranded DNA and RNA independently of the cold shock domain. In an in vitro translation system the C-tail domain of the protein inhibited translation YB-1 can form a homodimer. We also characterized an intrinsic 3'-->5' DNA exonuclease activity of the protein. Our findings suggest that YB-1 functions in regulating DNA/RNA transactions.
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