Comprehensive screening of glycolysis-related genes by synthetic lethality
| Project/Area Number |
24591313
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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 |
Metabolomics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | がん / 解糖系 / スクリーニング / ユビキチンリガーゼ / ミトコンドリア / shRNAライブラリー |
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| Outline of Final Research Achievements |
Glycolysis is a vital metabolic system. However, our understanding on glycolysis remains limited. To identify new genes involved in glycolysis regulation, we have performed a genome-wide gene knockdown analysis in human lung carcinoma PC8 cells using a mitochondrial inhibitor oligomycin and an shRNA library carried by a lentiviral vector, and finally identified five genes. Among them, we further focused on RNF126. RNF126 was found to act as a ubiquitin ligase for PDKs, resulting in their proteasomal degradation. This decrease in PDK levels allowed pyruvate dehydrogenases to catalyze the conversion of pyruvate to acetyl CoA. Moreover, depletion of RNF126 in cancer cells suppressed colony formation in soft agar as well as tumorigenicity in mice. RNF126 expression was found to be under the control of the ERK signaling pathway, which is essential for anoikis resistance. Thus, RNF126 is an attractive molecule for treating cancer by selectively targeting anchorage-independent growth.
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Report
(5 results)
Research Products
(55 results)
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[Journal Article] MT1-MMP plays a critical role in henatopoiesis by regulating HIF-mediated chemo-/cytokine gene transcription within niche cells.2012
Author(s)
Chiemi Nishida, Kaori Kusubata, Yoshihiko Tashiro, Ismael Gritli, Aki Sato, Makiko Ohki-Koizumi, Yohei Morita, Makoto Nagano, Takeharu Sakamoto, Naohiko Koshikawa, Takahiro Kuchimaru, Shinae Kizaka-Kondoh, Motoharu Seiki, Hiromitsu Nakauchi, Beate Heissig, and Koichi Hattori.
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Journal Title
Blood
Volume: 119
Issue: 23
Pages: 5404-5416
DOI
Related Report
Peer Reviewed
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[Presentation] Control of metastatic niche formation by targeting APBA3/Mint3 in inflammatory monocytes2016
Author(s)
Toshiro Hara, Hiroki J. Nakaoka, Kouhei Mimura, Daisuke Hoshino, Masahiro Inoue, Fumitaka Nagamura, Yoshinori Murakami, Motoharu Seiki, and Takeharu Sakamoto
Organizer
Tenth AACR-Japanese Cancer Association Joint Conference
Place of Presentation
Hyatt Regency Maui (Maui, HI, USA)
Year and Date
2016-02-17
Related Report
Int'l Joint Research
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