Small Ubiquitin-related Modifier is Involved in Regulatory Mechanisms of DNA Repair and/or Gene Expression in Pancreatic Acinar Cells.
| Project/Area Number |
15590709
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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 |
Gastroenterology
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| Research Institution | Institute for Developmental Research, Aichi Human Service Center |
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Principal Investigator |
INAGUMA Yutaka Institute for Developmental Research, Aichi Human Service Center, Department of Molecular Neurobiology, Senior Researcher, 神経制御学部, 主任研究員 (10250250)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Hidenori Institute for Developmental Research, Aichi Human Service Center, Department of Molecular Neurobiology, Researcher, 神経制御学部, 研究員 (40311443)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | SUMO / TTRAP / Ubiquitin / APEX / DNA repair / Pancreas / Acinar cells / TDG |
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| Research Abstract |
A family of small ubiquitin-like modifier(SUMO) is a post-translational modification protein consists of four members, SUMO-1,-2,-3 and -4. In our previous observation, free SUMO-1 and -3 were enriched in pancreas. SUMO pathway is similar to the ubiquitin pathway but distinct E1,E2,and E3 enzymes are involved. SUMO is activated by heterodimeric E1 enzyme (AOS1 and UBA2). UBC9,an E2 enzyme, specifically conjugates SUMO to target proteins. Several E3 ligases for SUMO enhance sumoylation of target proteins. Sumoylation regulates various cellular processes including subcelluar compartmentalization, nuclear transport, signal transduction, transcription, replication, and DNA repair. To investigate roles of SUMO-3,we carried out yeast two-hybrid screening by using SUMO-3gg as bait and we isolated TTRAP (TRAF and TNF receptor-associated protein). A nuclear localization signal was present in the N-terminal region of TTRAP. The C-terminal structure of TTRAP was similar to the catalytic domain of AP endonuclease 1 (APEX). TTRAP also interacted with UBC9,p53,and PCNA in the two-hybrid assays. APEX coordinates with thymine DNA glycosylase(TDG) to repair DNA lesions. Sumoylation of TDG is involved in turnover of this enzyme. TTRAP bound to double stranded DNA in a TDG-dependent manner. Together, our results suggested that SUMO-3 and TTRAP might be involved in DNA repair and/or control of transcription.
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Report
(3 results)
Research Products
(10 results)
