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Uesugi Laboratory

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Create New World of Bioactive Synthetic Molecules
New ways to use, New Shapes, New sizes.

As biological processes all stem from chemical events, it should be possible to understand or manipulate biological events by using chemistry. As chemical biologists our challenge is to discover or design unique organic molecules, 'super tools' that modulate fundamental processes in human cells. Using these 21st century super tools we can explore complex cellular events. Our job is creation: designing a new world of bioactive synthetic molecules, with unique and novel uses, forms and sizes. The future for small-molecule applications is open before us, in a range of fields, including future drug discovery and cell therapy. Our 21st century technology and skills will revolutionize the fight against the most difficult diseases and medical challenges of the age.

ケミカルバイオロジー~化学を起点とした生物学

ケミカルバイオロジーとは、化学を起点とした生物学です。生命の営みはせんじつめれば化学反応でできています。逆に化学を使って生命現象を理解したり、操ることができるはず。私たちの研究室では、生き物やヒト細胞にユニークな効果を及ぼす独自な有機化合物を見つける、もしくはデザインし、それらを道具として生命現象を探究・操作してきました。生物の仕組みは複雑ですが、有機化合物を起爆剤として用いることで、新たな切り口で生物を研究したり操作することができます。私たちの大きな研究目標は、生理活性合成化合物の新しい世界を切り開くことです。生理活性化合物の新しい利用法、新しいカタチをした生理活性化合物、新しいサイズの生理活性化合物など、アイデアを与えることができればと思うのです。こういったアイデアは、未来の創薬の考え方や化合物の細胞治療への利用などに結びつくはずです。


Selected Publications

Chemoproteomic Identification of Blue-Light-Damaged Proteins

Toh, K., Nishio, K., Nakagawa, R., Egoshi, S., Abo, M., Perron, A., Sato, S., Okumura, N., Koizumi, N., Dodo, K., Sodeoka, M., Uesugi, M.

J. Am. Chem. Soc. 144(44), 20171–20176 (2022)
https://doi.org/10.1021/jacs.2c07180

(2022) Chemoproteomic Identification of Blue-Light-Damaged Proteins.jpg



Self-assembling small-molecule adjuvants as antigen nano-carriers

Jin, S., Zhuo, S., Takemoto, Y., Li, Y., Uesugi, M.

Chem. Comm. 58, 12228-12231 (2022)
https://doi.org/10.1039/D2CC05016A

(2022) Self-assembling small-molecule adjuvants as antigen nano-carriers.png



Magnetic Control of Cells by Chemical Fabrication of Melanin

Nishio, K., Toh, K., Perron, A., Goto, M., Abo, M., Shimakawa, Y., Uesugi, M.

J. Am. Chem. Soc. 144(37), 16720–16725 (2022)
https://doi.org/10.1021/jacs.2c06555

(2022)Magnetic Control of Cells by Chemical Fabrication of Melanin.jpg



Discovery of a phase-separating small molecule that selectively sequesters tubulin in cells

Ado, G., Noda, N., Vu, H., Perron, A., Mahapatra, A., Arista, K., Yoshimura, H., Packwood, D., Ishidate, F., Sato, S., Ozawa, T., Uesugi, M.

Chemical Science 13, 5760-5766 (2022)
https://doi.org/10.1039/D1SC07151C

(2022) Discovery of a phase-separating small molecule that selectively sequesters tubulin in cells.jpg



Glucose as a Protein-Condensing Cellular Solute

Noda, N., Jung, Y., Ado, G., Mizuhata, Y., Higuchi, M., Ogawa, T., Ishidate, F., Sato, S., Kurata, H., Tokitoh, N., Uesugi, M.

ACS Chem. Biol. 17(3), 567–575 (2022)
https://doi.org/10.1021/acschembio.1c00849

(2022)Glucose as a Protein-Condensing Cellular Solute.gif



Discovery of Non-Cysteine-Targeting Covalent Inhibitors by Activity-Based Proteomic Screening with a Cysteine-Reactive Probe

Jung, Y., Noda, N., Takaya, J., Abo, M., Toh, K., Tajiri, K., Cui, C., Zhou, L., Sato, S., Uesugi, M.

ACS Chem. Biol. 17(2), 340–347 (2022)
https://doi.org/10.1021/acschembio.1c00824

(2022)Discovery of Non-Cysteine-Targeting Covalent Inhibitors.gif



Controlled lipid β-oxidation and carnitine biosynthesis by a vitamin D metabolite.

Mendoza, A., Takemoto, Y., Cruzado, K., Masoud, S., Nagata, A., Tantipanjaporn, A., Okuda, S., Kawagoe, F., Sakamoto, R., Odagi, M., Mototani, S., Togashi, M., Kawatani, M., Aono, H., Osada, H., Nakagawa, H., Higashi, T., Kittaka, A., Nagasawa, K., Uesugi, M.

Cell Chemical Biology 29(4), 660-669 (2022)
https://doi.org/10.1016/j.chembiol.2021.08.008

(2021) Controlled lipid β-oxidation and carnitine biosynthesis by a vitamin D metabolite.jpg



Chemical Genetics Reveals a Role of Squalene Synthase in TGFβ Signaling and Cardiomyogenesis

Takemoto, Y., Kadota, S., Minami, I., Otsuka, S., Okuda, S., Abo, M., Punzalan, L., Shen, Y., Shiba, Y., Uesugi, M.

Angew. Chem. Int. Ed. 60(40), 21824-21831 (2021)
https://doi.org/10.1002/anie.202100523

(2021) Chemical Genetics Reveals a Role of Squalene Synthase in TGFβ Signaling and Cardiomyogenesis.png



Non-genetic cell-surface modification with a self-assembling molecular glue.

Hakariya, H., Takashima, I., Takemoto, M., Noda, N., Sato, S., Uesugi, M.

Chem. Comm. 57(12), 1470-1473 (2021)
https://doi.org/10.1039/d0cc07171d

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Discovery of Self‐Assembling Small Molecules as Vaccine Adjuvants.

Jin, S., Vu, H., Hioki, K., Noda, N., Yoshida, H., Shimane, T., Ishizuka, S., Takashima, I., Mizuhata, Y., Pe, K., Ogawa, T., Nishimura, N., Packwood, D., Tokitoh, N., Kurata, H., Yamasaki, S., Ishii, K., Uesugi, M.

Angew. Chem. Int. Ed. 60(2), 961-969 (2021)
https://doi.org/10.1002/anie.202011604

(2020) Discovery of Self‐Assembling Small Molecules as Vaccine Adjuvants.png



Chemoproteomic Profiling of a Pharmacophore-Focused Chemical Library.

Punzalan, L., Jiang, L., Mao, D., Mahapatra, A., Sato, S., Takemoto, Y., Tsujimura, M., Kusamori, K., Nishikawa, M., Zhou, L., Uesugi, M.

Cell Chemical Biology 27(6), 708–718 (2020)
https://doi.org/10.1016/j.chembiol.2020.04.007

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Discovery of a Small-Molecule-Dependent Photolytic Peptide.

Takemoto, Y., Mao, Di., Punzalan, L., Götze, S., Sato, S., Uesugi, M.

J. Am. Chem. Soc. 142(3), 1142-1146 (2020)
https://doi.org/10.1021/jacs.9b09178

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Synthetic Chemical Probes That Dissect Vitamin D Activities.

Nagata, A., Akagi, Y., Asano, L., Kotake, K., Kawagoe, F., Mendoza, A., Masoud, S., Usuda, K., Yasui, K., Takemoto, Y., Kittaka, A., Nagasawa, K., Uesugi, M.

ACS Chem. Biol. 14(12), 2851–2858 (2019)
https://doi.org/10.1021/acschembio.9b00718

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Nutrient-Based Chemical Library as a Source of Energy Metabolism Modulators.

Furuta,T., Mizukami, Y., Asano, L., Kotake, K., Ziegler, S., Yoshida, H., Watanabe, M., Sato, S., Waldmann, H., Nishikawa, M., Uesugi, M.

ACS Chem. Biol. 14(9), 1860-1865 (2019)
https://doi.org/10.1021/acschembio.9b00444

Nutrient-Based Chemical Library as a Source of Energy Metabolism Modulators.png



Multifunctionalization of cells with a self-assembling molecule to enhance cell engraftment.

Takashima, I., Kusamori, K., Hakariya, H., Takashima, M., Vu, TH., Mizukami, Y., Noda, N., Takayama, Y., Katsuda, Y., Sato, S., Takakura, Y., Nishikawa, M., Uesugi, M.

ACS Chem. Biol., 14(4), 775–783 (2019)
https://doi.org/10.1021/acschembio.9b00109

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Small-molecule screening yields a compound that inhibits the cancer-associated transcription factor Hes1 via the PHB2 chaperone.

Perron, A., Nishikawa, Y., Iwata, J., Shimojo, H., Takaya, J., Kobayashi, K., Imayoshi, I., Mbenza, N. M,, Takenoya, M., Kageyama, R., Kodama, Y., Uesugi, M.

J. Biol. Chem. 293(21), 8285-8294 (2018)
https://doi.org/10.1074/jbc.RA118.002316

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Chemical decontamination of iPS cell-derived neural cell mixtures.

Mao, D., Chung, X. K. W., Andoh-Noda, T., Qin, Y., Sato, S., Takemoto, Y., Akamatsu, W., Okano, H., Uesugi, M.

Chem. Commun. 54, 1355-1358 (2018)
https://doi.org/10.1039/C7CC08686E

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Vitamin D metabolite, 25-Hydroxyvitamin D, regulates lipid metabolism by inducing degradation of SREBP/SCAP.

Asano, L., Watanabe, M., Ryoden, Y., Usuda, K., Yamaguchi, T., Khambu, B., Takashima, M., Sato, S., Sakai, J., Nagasawa, K., Uesugi, M.

Cell Chem Biol. 24, 207-217 (2017)
https://doi.org/10.1016/j.chembiol.2016.12.017

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A synthetic hybrid molecule for the selective removal of human pluripotent stem cells from cell mixtures.

Mao, D., Ando, S., Sato, S., Qin, Y., Hirata, N., Katsuda, Y., Kawase, E., Kuo, T.F., Minami, I., Shiba, Y., Ueda, K., Nakatsuji, N., Uesugi, M.

Angew. Chem. Int. Ed. 56(7), 1765-1770 (2017)
https://doi.org/10.1002/anie.201610284

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A small molecule that represses translation of G-quadruplex-containing mRNA.

Katsuda, Y., Sato, S., Asano, L., Morimura, Y., Furuta, T., Sugiyama, H., Hagihara, M., Uesugi, M.

J. Am. Chem. Soc. 138, 9037-9040 (2016)
https://doi.org/10.1021/jacs.6b04506

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A potent and site-selective agonist of TRPA1.

Takaya, J., Mio, K., Shiraishi, T., Kurokawa, T., Otsuka, S., Mori, Y., Uesugi, M.

J. Am. Chem. Soc. 137, 15859−15864 (2015)
https://doi.org/10.1021/jacs.5b10162

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Intracellular generation of a diterpene-peptide conjugate that inhibits 14-3-3-mediated interactions.

Parvatkar, P., Kato, N., Uesugi, M., Sato, S., Ohkanda, J.

J. Am. Chem. Soc. 137, 15624-15627 (2015)
https://doi.org/10.1021/jacs.5b09817

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Live-cell imaging of endogenous mRNAs with a small molecule.

Sato, S., Watanabe, M., Katsuda, Y., Murata, A., Wang, D. O., Uesugi M.

Angew. Chem. Int. Ed. 54(6), 1855-1858 (2015)
https://doi.org/10.1002/anie.201410339

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Synthetic molecules that protect cells from anoikis and their use in cell transplantation.

Frisco-Cabanos, H.L., Watanabe, M., Okumura, N., Kusamori, K., Takemoto, N., Takaya, J., Sato, S., Yamazoe, S., Takakura, Y., Kinoshita, S., Nishikawa, M., Koizumi, N., Uesugi, M.

Angew. Chem. Int. Ed. 53(42), 11208-11213 (2014)
https://doi.org/10.1002/anie.201405829

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Selective elimination of human pluripotent stem cells by a marine natural product derivative.

Kuo, T.F., Mao, D., Hirata, N., Khambu, B., Kimura, Y., Kawase, E., Shimogawa, H., Ojika, M., Nakatsuji, N., Ueda, K., Uesugi, M.

J. Am. Chem. Soc. 136 (28), 9798-9801 (2014)
https://doi.org/10.1021/ja501795c

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A chemical probe that labels human pluripotent stem cells.

Hirata, N., Nakagawa, M., Fujibayashi, Y., Yamauchi, K., Murata, A., Minami, I., Tomioka, M., Kondo, T., Kuo, T.F., Endo, H., Inoue, H., Sato, S., Ando, S., Kawazoe, Y., Aiba, K., Nagata, K., Kawase, E., Chang, Y.T., Suemori, H., Eto, K., Nakauchi, H., Yamanaka, S., Nakatsuji, N., Ueda, K., Uesugi, M.

Cell Rep 6., 1165–1174 (2014)
https://doi.org/10.1016/j.celrep.2014.02.006

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VMAT2 identified as a regulator of late-stage beta cell differentiation.

Sakano, D., Shiraki, N., Kikawa, K., Yamazoe, T., Kataoka, M., Umeda, K., Araki, K., Mao, D., Matsumoto, S., Nakagata, N., Andersson, O., Stainier, D., Endo, F., Kume, K., Uesugi, M., Kume, S.

Nat. Chem. Biol. 10, 141-148 (2014)
https://doi.org/10.1038/nchembio.1410

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Inhibition of microtubule assembly by a complex of actin and antitumor macrolide aplyronine A.

Kita, M., Hirayama, Y., Yoneda, K., Yamagishi, K., Chinen, T., Usui, T., Sumiya, E., Uesugi, M., Kigoshi, H.

J. Am. Chem. Soc. 135 (48), 18089-18095 (2013)
https://doi.org/10.1021/ja406580w

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Small molecule-induced clustering of heparan sulfate promotes cell adhesion.

Takemoto, N., Suehara, T., Frisco, H., Sato, S., Sezaki, T., Kusamori, K., Kawazoe, Y., Park, S., Yamazoe, S., Mizuhata, Y., Inoue, R., Miller, G., Hansen, S., Jayson, G., Gardiner, J., Kanaya, T., Tokitoh, N., Ueda, K., Takakura, Y., Kioka, N., Nishikawa, M., Uesugi, M.

J. Am. Chem. Soc. 135 (30), 11032-11039 (2013)
https://doi.org/10.1021/ja4018682

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A small molecule that promotes cardiac differentiation of human pluripotent stem cells under defined cytokine- and xeno-free conditions.

Minami, I., Yamada, K., Otsuji, T.G., Yamamoto, T., Shen, Y., Otsuka, S., Kadota, S., Morone, N., Barve, M., Asai, Y., Tenkova-Heuser, T., Heuser, J. E., Uesugi, M., Aiba, K., Nakatsuji, N.

Cell Rep. (5), 1448-1460 (2012)
https://doi.org/10.1016/j.celrep.2012.09.015

research13.jpg



Synthesis and evaluation of diarylthiazole derivatives that inhibit activation of sterol regulatory element-binding proteins.

Kamisuki, S., Shirakawa T., Kugimiya, A., Abu-Elheiga, L., Choo, H.-Y., Yamada, K., Shimogawa, H., Wakil, S. J., Uesugi, M.

J. Med. Chem. 54(13), 4923-4927 (2011)
https://doi.org/10.1021/jm200304y

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A mitochondrial surface-specific fluorescent probe activated by bioconversion.

Kawazoe, Y., Shimogawa, H., Sato, A., Uesugi, M.

Angew. Chem. Int. Ed. 50(24), 5478-5481 (2011)
https://doi.org/10.1002/anie.201100935

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Small-molecule fluorescent probes for specific RNA targets.

Murata, A., Sato, S., Kawazoe, Y., Uesugi, M.

Chem. Comm. 47(16), 4712-4714 (2011)
https://doi.org/10.1039/C1CC10393H

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Cell-morphology profiling of a natural product library identifies bisebromoamide and miuraenamide A as actin-filament stabilizers.

Sumiya, E., Shimogawa, H., Sasaki, H., Tsutsumi, M., Yoshita, K., Ojika, M., Suenaga, K., Uesugi, M.

ACS Chem. Biol. 6(5), 425-431 (2011)
https://doi.org/10.1021/cb1003459

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Deactivation of STAT6 through Serine 707 phosphorylation by JNK.

Shirakawa, T. Kawazoe, Y., Tsujikawa, T., Jung, D., Sato, S., Uesugi, M.

J. Biol. Chem. 286, 4003-4010 (2011)
https://doi.org/10.1074/jbc.M110.168435

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Marine natural product aurilide activates the OPA1-mediated apoptosis by binding to prohibitin.

Sato, S. Murata, A., Orihara, T., Shirakawa, T., Suenaga, K., Kigoshi, H., Uesugi, M.

Chem. Biol. 18 (1), 131-139 (2011)
https://doi.org/10.1016/j.chembiol.2010.10.017

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Biochemical target isolation for novices: Affinity-based strategies. (Review)

Sato, S. Murata, A., Shirakawa, T., Uesugi, M.

Chem. Biol. 17 (6), 616-623 (2010)
https://doi.org/10.1016/j.chembiol.2010.05.015

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A small molecule that blocks fat synthesis by inhibiting the activation of SREBP.

Kamisuki, S., Mao, Q., Abu-Eliheiga, L., Gu, Z., Kugimiya, A., Kwon, Y., Shinohara, T., Kawazoe, Y., Sato, S. Asakura, K., Choo, H., Sakai, J., Wakil, SJ., Uesugi, M.

Chem. Biol. 16 (8), 882-892 (2009)
https://doi.org/10.1016/j.chembiol.2009.07.007

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A dumbbell-shaped small molecule that promotes cell adhesion and growth.

Yamazoe, S., Shimogawa, H., Sato, S., Esko, J. D., Uesugi, M.

Chem. Biol. 16 (7), 773-782 (2009)
https://doi.org/10.1016/j.chembiol.2009.06.008

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Wrenchnolol derivative optimized for gene activation in cells.

Jung, D., Shimogawa, H., Kwon, Y., Mao, Q., Sato, S., Kamisuki, S., Kigoshi, H., Uesugi, M.

J. Am. Chem. Soc. 131(13), 4774-4782 (2009)
https://doi.org/10.1021/ja900669k

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Polyproline-rod approach to isolating protein targets of bioactive small molecules: isolation of a new target of indomethacin.

Sato, S., Kwon, Y., Kamisuki, S., Srivastava, N., Mao, Q., Kawazoe, Y., Uesugi, M.

J. Am. Chem. Soc. 129(4), 873-880 (2007)
https://doi.org/10.1021/ja0655643

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Chemical genetic identification of the IGF-linked pathway that is mediated by STAT6 and MFP2

Choi, Y., Shimogawa, H., Murakami, K., Ramdas, L., Zhang, W., Qin, J., Uesugi,M.

Chem. Biol, 13, 241-249 (2006)
https://doi.org/10.1016/j.chembiol.2005.12.011

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Chemical genetic identification of histamine receptor H1 as a stimulator of insulin-induced adipogenesis.

Kawazoe, Y., Tanaka, H., Uesugi, M.

Chem. Biol. 11, 907-913 (2004)
https://doi.org/10.1016/j.chembiol.2004.04.017

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Small molecule transcription factor mimic.

Kwon,Y., Arndt, H., Mao, Q., Choi, Y., Kawazoe, Y., Dervan, P. B., Uesugi, M.

J. Am. Chem. Soc. 126, 15940-15941 (2004)
https://doi.org/10.1021/ja0445140

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A wrench-shaped synthetic molecule that modulates a transcription factor-coactivator interaction.

Shimogawa, H., Kwon, Y., Mao, Q., Kawazoe, Y., Choi, Y., Asada, S., Kigoshi, H., & Uesugi, M.

J. Am. Chem. Soc. 126, 3461-3471 (2004)
https://doi.org/10.1021/ja038855+

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A gene-expression inhibitor that targets an alpha-helix-mediated protein interaction.

Asada, S., Choi, Y., & Uesugi, M.

J. Am. Chem. Soc. 125, 4992-4993 (2003)
https://doi.org/10.1021/ja0292703

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Identification of bioactive molecules by adipogenesis profiling of organic compounds.

Choi, Y., Kawazoe, Y., Murakami, K., Misawa, H., & Uesugi, M

J. Biol. Chem. 278, 7320-7324 (2003)
https://doi.org/10.1074/jbc.M210283200

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External control of Her2 expression and cancer cell growth by targeting a Ras-linked coactivator.

Asada, S., Choi, Y., Yamada, M., Wang, S., Hung, M., Qin, J., & Uesugi, M.

Proc. Natl. Acad. Sci. USA 99, 12747-12752 (2002)
https://doi.org/10.1073/pnas.202162199

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Divergent hTAF(II)31-binding motifs hidden in activation domains.

Choi, Y., Asada, S., & Uesugi, M.

J. Biol. Chem. 275, 15912-15916 (2000)
https://doi.org/10.1074/jbc.275.21.15912

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The alpha helical FXXphiphi motif in p53: TAF interaction and discrimination by MDM2.

Uesugi, M. & Verdine, G. L.

Proc. Natl. Acad. Sci. USA 96, 14801-14806 (1999)
https://doi.org/10.1073/pnas.96.26.14801

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A non-natural transcriptional coactivator.

Nyanguile, O., Uesugi, M., Austin, D. J., & Verdine, G. L.

Proc. Natl. Acad. Sci. USA 94, 13402-13406 (1997)
https://doi.org/10.1073/pnas.94.25.13402

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Induced alpha helix in the VP16 activation domain upon binding to a human TAF.

Uesugi, M., Nyanguile, O., Lu, H., Levine, A. J., & Verdine, G. L.

Science 277, 1310-1313 (1997)
https://doi.org/10.1126/science.277.5330.1310

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Last-modified: 2022-11-21 (月) 12:19:52 (73d)