Pathomechanism of cell death induced by N-terminal fragment of profilaggrin
Project/Area Number |
15K09740
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Dermatology
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Research Institution | University of Toyama |
Principal Investigator |
Makino Teruhiko 富山大学, 大学院医学薬学研究部(医学), 准教授 (90359711)
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Co-Investigator(Kenkyū-buntansha) |
清水 忠道 富山大学, 大学院医学薬学研究部(医学), 教授 (70260396)
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | profilaggrin / 表皮 / 角化 / 細胞死 / カルパイン / 表皮角化細胞 / DNA分解 / 皮膚癌 / アポトーシス |
Outline of Final Research Achievements |
Profilaggrin plays a critical role in keratinocyte terminal differentiation. During this process, a 55-kDa N-terminal fragment of profilaggrin (FLG-N) is translocated into the nucleus; thereafter, the cells became TUNEL-positive. We examined the molecular mechanism underlying the DNA degradation process induced by FLG-N in keratinocytes. Our findings suggest that calpine I and apoptosis-inducing factor may be associated with the FLG-N inducing-DNA degradation. We also found that FLG-N directly interacted with pinin, a transcriptional activator binding to the E-box 1 core sequence of the E-cadherin promoter gene, within the nucleus. Surprisingly, the suppression of pinin expression can induce cell death in keratinocytes even without interaction with FLG-N. In addition, 19 amino acids present in the N-terminal profilaggrin can induce cell death for squamous cell carcinoma (SCC) cell line HSC-1. We therefore hypothesized that FLG-N may be a novel therapeutic target in SCC.
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] RAC1 activation drives pathologic interactions between the epidermis and immune cells.2016
Author(s)
Winge MC, Ohyama B, Dey CN, Boxer LM, Li W, Ehsani-Chimeh N, Truong AK, Wu D, Armstrong AW, Makino T, Davidson M, Starcevic D, Kislat A, Nguyen NT, Hashimoto T, Homey B, Khavari PA, Bradley M, Waterman EA, Marinkovich MP.
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Journal Title
J Clin Invest.
Volume: 126
Issue: 7
Pages: 2661-77
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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