研究業績

主要論文（原著）Selected Publications

[ * = 責任著者 ]
  1. Endo A*, Fukushima T, Takahashi C, Tsuchiya H, Ohtake F, Ono S, Ly T, Yoshida Y, Tanaka K, Saeki Y*, Komada M*. USP8 prevents aberrant NF-κB and Nrf2 activation by counteracting ubiquitin signals from endosomes. J Cell Biol 223(3): e202306013. (2024) DOI: 10.1083/jcb.202306013
  2. Iriki T, Iio H, Yasuda S, Masuta S, Kato M, Kosako H, Hirayama S, Endo A, Ohtake F, Kamiya M, Urano Y, Saeki Y, Hamazaki J, Murata S*. Senescent cells form nuclear foci that contain the 26S proteasome. Cell Reports 42(8):112880 (2023) DOI: 10.1016/j.celrep.2023.112880
  3. Akizuki Y, Morita M, Mori Y, Kaiho-Soma A, Dixit S, Endo A, Shimogawa M, Hayashi G, Naito M, Okamoto A, Tanaka K, Saeki Y, Ohtake F.* cIAP1-based degraders induce degradation via branched ubiquitin architectures. Nature Chemical Biology 19 (3):311-322 (2023), DOI: https://doi.org/10.1038/s41589-022-01178-1
  4. Huang Y, Yokoe H, Kaiho-Soma A, Takahashi K, Hirasawa Y, Morita H, Ohtake F*, Kanoh N*. Design, Synthesis, and Evaluation of Trivalent PROTACs Having a Functionalization Site with Controlled Orientation. Bioconjug Chem 33 (1) :142-151 (2022) DOI: 10.1021/acs.bioconjchem.1c00490
  5. Okubo Y, Ohtake F, Igarashi K, Yasuhiko Y, Hirabayashi Y, Saga Y, Kanno J. Cleaved Delta like 1 intracellular domain regulates neural development via Notch signal dependent and independent pathways. Development 149 (19) :dev.193664. doi: 10.1242/dev.193664. (2021)
  6. Kaiho-Soma A., Akizuki Y., Igarashi K., Endo A., Shoda T., Kawase Y., Demizu Y., Naito M., Saeki Y., Tanaka K., Ohtake F*. TRIP12 promotes small molecule-induced degradation through K29/K48 branched ubiquitin chains. Molecular Cell, 81 (7) 1411-1424 (2021)
  7. Nakabayashi O, Takahashi H, Moriwaki K, Komazawa-Sakon S, Ohtake F, Murai S, Tsuchiya Y, Koyahara Y, Saeki Y, Yoshida Y, Yamazaki S, Tokunaga F, Sawasaki T, and Nakano H*. MIND bomb 2 prevents RIPK1 kinase activity-independent apoptosis through ubiquitylation of cFLIPL. Communications Biology, 4, 80, 2021
  8. Watanabe M*, Saeki Y, Takahashi H, Ohtake F, Yoshida Y, Kasuga Y, Kondo T, Yaguchi H, Suzuki M, Ishida H, Tanaka K, Hatakeyama S*. A substrate-trapping strategy to find E3 ubiquitin ligase substrates identifies Parkin and TRIM28 targets. Communications Biology, 3, 592, 2021
  9. Fuseya Y., Fujita H., Kim M., Ohtake F., Nishide A., Sasaki K., Saeki Y., Tanaka K., Takahashi R., Iwai K*. The HOIL-1L ligase modulates immune signaling and cell death via mono-ubiquitination of LUBAC. Nature Cell Biology, 22, 663-673, 2020
  10. Yasuda S, Tsuchiya H, Kaiho A, Guo Q, Ikeuchi K, Endo A, Arai N, Ohtake F, Murata S, Inada T, Baumeister W, Fernandez-Busnadiego R, Tanaka K*, and Saeki Y*. Stress - and ubiquitylation-dependent phase separation of the proteasome. Nature, 578, 296-300, 2020
  11. Oikawa D., Sato Y., Ohtake F., Komakura K., Hanada K., Sugawara K., Terawaki S., Mizukami Y., Phuong HT., Iio K., Obika S., Fukushi M., Irie T., Tsuruta D., Sakamoto S., Tanaka K., Saeki Y., Fukai S., and Tokunaga F. Molecular bases for HOIPIN-mediated inhibition of LUBAC and innate immune responses. Communications Biology, 3, 163, 2020
  12. Ohtake, F., Tsuchiya, H., Tanaka, K., and Saeki, Y*. Methods to measure ubiquitin chain length and linkage. Methods in Enzymology, 618:105-133, 2019 (Impact Factor: 0.83)
  13. Ohtake, F.*, Tsuchiya, H., Saeki, Y., and Tanaka, K*. K63 ubiquitylation triggers proteasomal degradation by seeding branched ubiquitin chains. Proc Natl Acad Sci USA 115, E1401-E1408, 2018
  14. Tsuchiya, H., Burana, D., Ohtake, F., Arai, N., Kaiho, A., Komada, M., Tanaka,K.*, and Saeki, Y*. Ub-ProT reveals global length and composition of protein ubiquitylation in cells. Nature Commun 9, 524, 2018
  15. Tsuchiya, H., Ohtake, F., Arai, N., Kaiho, A., Yasuda, S., Tanaka, K.*, and Saeki, Y*. In Vivo Ubiquitin Linkage-type Analysis Reveals that the Cdc48-Rad23/Dsk2 axis contributes to K48-linked chain specificity of the proteasome. Molecular Cell 66, 488-502, 2017
  16. Ohtake, F.*, Saeki, Y., Ishido, S., Kanno, J., and Tanaka, K*. The K48-K63 branched ubiquitin chain regulates NF-κB signaling. Molecular Cell 64, 251-266, 2016
  17. Okada, M., Ohtake, F., Nishikawa, H., Wu, W., Saeki, Y., Takana, K., and Ohta, T*. Liganded ERα stimulates the E3 ubiquitin ligase activity of UBE3C to facilitate cell proliferation. Mol Endocrinol 29, 1646-57, 2015
  18. Ohtake, F.*, Saeki, Y., Sakamoto, K., Ohtake, K., Nishikawa, H., Tsuchiya, H., Ohta, T., Tanaka, K., and Kanno, J. Ubiquitin acetylation inhibits polyubiquitin chain elongation. EMBO Rep 16,192-201, 2015

主要総説Selected Reviews

[ * = 責任著者 ]
  1. Neal S, Ohtake F, Cuervo AM, Hegde RS, Jakob U, Lazarou M, Gilbert WV, Chen ZJ, Tooze SA, Haber JE, Walters KJ, Hartl FU. Quality Control: Maintaining molecular order and preventing cellular chaos. Molecular Cell. (2022) 82 (8) :1390-1397. doi: 10.1016/j.molcel.2022.04.002.
  2. Ohtake F*. Branched ubiquitin code: from basic biology to targeted protein degradation. J Biochem, 171 (4) : 361-366, (2022) doi: 10.1093/jb/mvac002
  3. Ohtake, F.* Mass spectrometry technologies for deciphering the ubiquitin code. Trends in Biochemical Sciences, 45, 820-821, 2020
  4. 大竹史明「分岐型ユビキチン鎖とアセチル化ユビキチン」生化学 92 (1) pp.57-63, 2020
  5. Ohtake F*, Tsuchiya H. The emerging complexity of ubiquitin architecture. J Biochem, 161, 125-133, 2017
  6. 大竹史明「ユビキチン鎖とNF-κB活性化」臨床免疫・アレルギー科 68 (5), 569-575, 2017
  7. 佐伯 泰、土屋光、大竹史明、田中啓二: Update review「UPSの未解決問題に挑む～ついに明かされるプロテアソーム分解の制御機構」実験医学35, 2756－2763, 2017
  8. 土屋 光、大竹史明、田中啓二、佐伯泰「Cdc48-Rad23/Dsk2軸はプロテアソームに依存的なタンパク質分解のおける主要な経路である」ライフサイエンス新着論文レビュー (DOI: 10.7875/first.author.2017.055) 2017
  9. 大竹史明、佐伯 泰、田中啓二「Current Topics: リジン48/63分岐型ユビキチン鎖はNF-κB経路の調節因子である」実験医学 35, 452-454, 2017
  10. 大竹史明：「分岐型ユビキチンの定量方法の構築」新学術領域研究「ユビキチンネオバイオロジー：拡大するタンパク質制御システム」領域ニュースレターVol.5, 4-6, 2017
  11. 大竹史明、佐伯泰、田中啓二「K48/K63分岐型のユビキチン鎖はNF-κBシグナルを制御する」ライフサイエンス新着論文レビュー (DOI: 10.7875/first.author.2016.109) 2016

受賞Awards

  • 令和4年度科学技術分野の文部科学大臣表彰（科学技術賞）2022年
  • 平成30年度東京都医学総合研究所職員表彰（理事長賞）2019年

主な招待講演（直近2年）Invited Lecture

  • 第96回日本生化学大会シンポジウム (2023.11.2)
  • 日本薬学会第38回創薬セミナー（2023.7.12）
  • 国際学会 Cold Spring Harbor Laboratory Meeting. Ubiquitins, Autophagy & Disease (2023.4.25-29 米国)
  • 国際シンポジウム 'Ubiquitin New Frontier' (2022.12.3)
  • 第95回日本生化学会大会シンポジウム (2022.11.11)
  • 日本ケミカルバイオロジー学会第16回年会シンポジウム (2022.6.1)
  • Dana-Farber Cancer Institute "Targeted Protein Degradation Webinar Series" (2022.2.4 米国)
  • 第44回日本分子生物学会年会シンポジウム (2021.12.2)
  • 第94回日本生化学大会シンポジウム (2021.11.3)
  • 第40回日本認知症学会学術集会 (2021.11.26-28)
  • 日本プロテオーム学会2021年大会 (2021.7.20-21)
  • 第25回日本がん分子標的治療学会学術集会 (2021.5.26)
  • 国際学会 Cold Spring Harbor Laboratory Meeting. Ubiquitin, Autophagy & Disease (2021.4.27-30 米国)