Regulatory mechanism of p62 gene expression
| Project/Area Number |
23500434
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
MATSUMOTO Gen 独立行政法人理化学研究所, 脳科学総合研究センター, 客員研究員 (50415303)
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| Project Period (FY) |
2011-04-28 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | タンパク質分解 / 選択的オートファジー / p62 / SQSTM1 / 薬剤スクリーニング / レポーター / レポーターアッセイ / リン酸化 / 薬剤ライブラリー |
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| Outline of Final Research Achievements |
p62/Sqstm1 is a key molecule for the selective autophagy. To investigate how to induce p62 in cells, we performed a drug screening that activated or inactivated p62 promoter. For this aim, we cloned human 1.8 kbp of p62 promoter region and inserted GFP gene under the predicted translation starting points. Using this reporter constructs, we identified five p62-inducer candidates. Two of them were obviously able to reduce polyglutamine aggregation in cells, but the S403-phospholylated p62 were not accumulated. On the other hand, one of the five candidates enhanced the polyglutamine aggregate formation and the accumulation of S403-phospho-p62. This may be possible that the drug may interfere the constitutive autophagy. Our results suggests that p62 promoter can be modulated artificially and the appropriate induction of p62 may be beneficial to induce selective autophagy.
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Report
(5 results)
Research Products
(15 results)
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[Journal Article] Depletion of p62 reduces nuclear inclusions and paradoxically ameliorates disease phenotypes in Huntington's model mice.2015
Author(s)
4)Kurosawa M, Matsumoto G, Kino Y, Okuno M, Kurosawa-Yamada M, Washizu C, Taniguchi H, Nakaso K, Yanagawa T, Warabi E, Shimogori T, Sakurai T, Hattori N, Nukina N.
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Journal Title
Hum Mol Genet.
Volume: 24
Issue: 4
Pages: 1092-105
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Dysregulation of the Proteasome Enhances the Toxicity of ALS-linked Mutant SOD12014
Author(s)
Kitamura, A., Inada, N., Kubota, H., Matsumoto, G., Kinjo, M., Morimoto, R.I., Nagata, K
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Journal Title
Genes to Cells
Volume: 3
Issue: 3
Pages: 209-224
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] NF-Y inactivation causes atypical neurodegeneration characterized by ubiquitin and p62 accumulation and endoplasmic reticulum disorganization2014
Author(s)
Yamanaka, T., Tosaki, A., Kurosawa, M., Matsumoto, G., Koike, M., Uchiyama, Y., Maity, S.N., Shimogori, T., Hattori, N. & Nukina, N.
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Journal Title
Nat. Commun.
Volume: 5
Issue: 1
Pages: 3354-3354
DOI
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Peer Reviewed
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[Presentation] Phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated protein2011
Author(s)
Matsumoto, G., Wada, K., Okuno, M., Kurosawa, M., and Nukina, N.
Organizer
The 2011 Cold Spring Harbor Laboratory meeting on "The Ubiquitin Family"
Place of Presentation
Cold Spring Harbor, NY, USA
Related Report
