2004 Fiscal Year Final Research Report Summary
Elucidation of the molecular mechanisms of carcinogenesis by the VHL, tumor suppressor gene
| Project/Area Number |
13470041
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Kochi University |
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Principal Investigator |
ASO Teijiro Kochi University, Faculty of Medicine, Professor, 医学部, 教授 (20291289)
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| Co-Investigator(Kenkyū-buntansha) |
KITAJIMA Shigetaka Tokyo Medical and Dental University, Medical Research Institute, Professor, 難治疾患研究所, 教授 (30186241)
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| Project Period (FY) |
2001 – 2004
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| Keywords | Elongin / Transcription elongation / VHL tumor suppressor gene / RNA polymerase II / Gene targeting / ES cell |
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| Research Abstract |
1.Generation and characterization of Elongin A-deficient ES cells
To investigate the function of Elongin A in vivo, the two alleles of the Elongin A gene have been disrupted by homologous recombination in murine embryonic stem(ES) cells. The Elongin A-deficient ES cells are viable, but possess markedly enlarged cell mass and show a slow growth phenotype because they undergo a delayed mitosis. The cDNA microarray and RNase protection assay using the wild-type and Elongin A-deficient ES cells indicate that the expression of only a small subset of genes is significantly affected in the mutant cells. These findings suggest that Elongin A regulates transcription of a subset but not all of genes, and reveal a linkage between Elongin A function and cell cycle progression.
2.Identification of a novel transcription elongation factor, Elongin A3
We have identified a novel transcription elongation factor, Elongin A3. Mechanistic studies have demonstrated that Elongin A3 stimulate the rate of transcription elongation by RNA polymerase II and is capable of forming a stable complex with Elongin BC. In contrast to Elongin A, however, its transcriptional activity is not activated by Elongin BC. Structure-function analysis using fusion proteins composed of Elongin A3 and Elongin A revealed that the COOH-terminal region of Elongin A is important for the activation by Elongin BC.
3.Identification of EloA-BP1, a novel Elongin A binding protein with an exonuclease homology domain
We have identified a novel protein, termed EloA-BP1, which interacts with the NH2-termini of both Elongin A and SII. EloA-BP1 is composed of 1221 amino acids and its mRNA is expressed ubiquitously. As EloA-BP1 possesses the exonuclease domain at its COOH-terminus, this protein may have role to maintain the fidelity of transcriptional products.
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Research Products
(10 results)
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[Book] 臨床検査2004
Author(s)
田村 賢司
Total Pages
9
Publisher
医学書院
Description
「研究成果報告書概要(和文)」より
