Functional analysis of the role of FancD2 deubiquitination in response to DNA damage
| Project/Area Number |
18590306
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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 | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
MATSUSHITA Nobuko Tokyo University of Pharmacy and Life Science, School of Life Sciences, lecturer (30333222)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | DNA repair / mono-ubiauitination / de-ubiq uitination / Fanconi anemia / FancD2 |
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| Research Abstract |
Fanconi anemia is a rare, inherited disorder associate early-onset bone marrow failure, cancer predisposition, and genetic instability, which is characterized by a hypersensitivity to DNA-damaging agents, chromosome instability and overproduction of the myelosuppressive cytokines like TNF-α. Thirteen FA genes were identified, and eight of them, including FancL which has been ubiqutin ligase activity, form a nuclear complex, whole integrity is required for the monoubiquitination of the FA proteins FANCD2 and FANCI in response to DNA damage. We found that FancL induced monoubiquitination of FancD2 is required in DNA damage response, But the function of mono-ubuquitinated FANCD2 is not still unknown.
To identify its function, we performed yeast two-hybrid (Y2H) screens using ubiquitin fusion N-terminal chicken (ch) FancD2 as a bait. We have identified chTaxl-binding protein 1 (TAX1BP1), the ubiquitin fusion FandD2 binding protein. We also found that ectopically expressed FancD2 interacted with TAX1BP1 through monoubiquitination. TAX1BP1 is a negative regulator of TNF-a-and IL-1B-induced NF-KB activation and that binding to mono- and polyubiquitin by a ubiquitin-binding Zn finger domain in TAX1BP1. Our finding suggests that monoubiquitinated FancD2 binds to TAX1Bp 1, and they play inhibitory role in NF-KB induced overproduction of cytokines
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Report
(3 results)
Research Products
(8 results)
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[Journal Article] A requirement of FancL and FancD2 monoubiquitination in DNA repair2007
Author(s)
Seki, S., Ohzeki, M., Uchida, A., Hirano, S., Matsushita, N., Kitao, H., Oda, T., Yamashita, T., Kashihara, N., Tsubahara, A., Takata, M., Ishiai, M
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Journal Title
Genes Cells 12
Pages: 299-310
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] The Fanconi anemia pathway promotes homologous recombination repair in DT40 cell line.2006
Author(s)
Takata, M., Yamamoto, K., Matsushita, N., Kitao, H., Hirano, S., Ishiai, M
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Journal Title
Subcell Biochem 40
Pages: 295-311
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Functional interplay between BRCA2/FancD1 and FancC in DNA repair2006
Author(s)
Kitao, H., Yamamoto, K., Matsushita, N., Ohzeki, M., Ishiai, M., Takata, M
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Journal Title
J Biol Chem 281
Pages: 21312-20
Description
「研究成果報告書概要(欧文)」より
Related Report
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