Faculty Information, Institute for Chemical Research, Kyoto University   [ English | Japanese ]


UESUGI, Motonari

Division of Biochemistry - Chemical Biology -
（Laboratory in the Graduate School of Medicine）
Professor
Ph. D.
URL:
E-mail: uesugi@scl.kyoto-u.ac.jp
Tel: 0774-38-3225
Fax: 0774-38-3226
Academic career
    1990.4-1995.3Ph.D. degree in Pharmaceutical Chemistry and Biochemistry,Kyoto University
    1995.4-1998.8Postdoctoral Training in Chemical Biology,Harvard University
    1998.9-2005.2Assistant Professor, Department of Biochemistry, Baylor College of Medicine
    2005.2-presentAssociate Professor, Department of Biochemistry, Baylor College of Medicine
    2005.4-presentProfessor, Kyoto University, Institute for Chemical Research
    2007.10-presentProfessor, Kyoto University, Institute for Integrated Cell-Material Sciences
Research field
    Chemical Biology
Current research
  1. Small-molecule initiated biology
Selected publications
  1. Uesugi, M., Sekida, T., Matsuki, S., Sugiura, Y., Selective DNA cleavage by elsamicin A and switch function of its amino sugar group Biochemistry 30, 6711-6715 (1991).
  2. Uesugi, M., Sugiura, Y., Switch-function of amino sugar on elsamicin A, a DNA binding antitumor antibiotic Nucleic Acids Symp Ser. 22, 33-4 (1990).
  3. Sugiura, Y., Arakawa, T., Uesugi, M., Shiraki, T., Ohkuma, H., Konishi, M., Reductive and nucleophilic activation products of dynemicin A with methyl thioglycolate. Rational mechanism for DNA cleavage of thiol-activated dynemicin A Biochemistry 30, 2989-2992 (1991).
  4. Hirama, M., Gomibuchi, T., Fujiwara, K., Sugiura, Y., Uesugi, M., Synthesis and DNA-cleaving abilities of functional neocarzinostatin chromophore analogues. Base discrimination of a simple alcohol J. Am. Chem. Soc. 113, 9851-9853 (1991).
  5. Uesugi, M., Sugiura, Y., DNA cleaving modes in minor groove of DNA helix by esperamicin and calicheamicin antitumor antibiotics. Nucleic Acids Symp Ser. 27, 1-2 (1992).
  6. Owa, T., Haupt, A., Otsuka, M., Kobayashi, S., Tomioka, N., Itai, A., Ohno, M., Shiraki, T., Uesugi, M., Sugiura, Y., Man-designed bleomycins: significance of the binding sites as enzyme models and of stereochemistry of the linker moiety Tetrahedron 48, 1193-1208 (1992).
  7. Uesugi, M., Sugiura, Y., Product analyses in DNA strand scission by antitumor antibiotic elsamicin A Biochem. Biophys. Res. Commun. 186, 580-587 (1992).
  8. Shiraki, T., Uesugi, M., Sugiura, Y., C-1' hydrogen abstraction of deoxyribose in DNA strand scission by dynemicin A Biochem. Biophys. Res. Commun. 188, 584-589 (1992).
  9. Uesugi, M., Kusakabe, T., Sugiura, Y., Induced-fit association between DNA and esperamicin. Importance of structural flexibility in host DNA duplex Nucleic Acids Symp Ser. 29, 89-90 (1993).
  10. Tokuda, M., Fujiwara, K., Gomibuchi, T., Hirama, M., Uesugi, M., Sugiura, Y., Synthesis of a hybrid molecule containing neocarzinostatin chromophore analogue and minor groove binder Tetrahedron Letters 34, 669-672 (1993).
  11. Uesugi, M., Sugiura, Y., New insights into sequence-recognition process of esperamicin A1 and calicheamicin g1I: origin of their selectivities and "induced fit" mechanism Biochemistry 32, 4622-4627 (1993).
  12. Kusakabe, T., Maekawa, K., Ichikawa, A., Uesugi, M., Sugiura, Y., Conformation-selective DNA strand breaks by dynemicin: A molecular wedge into flexible regions of DNA Biochemistry 32, 11669-11675 (1993).
  13. Kushida, T., Uesugi, M., Sugiura, Y., Kigoshi, H., Tanaka, H., Hirokawa, J., Ojika, M., Yamada, K., DNA damage by ptaquiloside, a potent bracken carcinogen: detection of selective strand breaks and identification of DNA cleavage products J. Am. Chem. Soc. 116, 479-486 (1994).
  14. Uesugi, M., Kusakabe, T., Sugiura, Y., Hydrophobic DNA binding of esperamicin requires conformational distortion of the host DNA Biochimi. Biophys. Acta 1261, 99-106 (1995).
  15. Totsuka, R., Aizawa, Y., Uesugi, M., Okuno, Y., Matsumoto, T., Sugiura, Y., RNA cleavage by C-1027 chromophore, an enediyne antitumor antibiotic: high selectivity to an anticodon arm Biochem. Biophys. Res. Commun. 208, 168-173 (1995).
  16. Kusakabe, T., Uesugi, M., Sugiura, Y., Sequence preference for strand cleavage of gapped duplexes by dynemicin A: possible mechanism of sequence-dependent double-stranded breaks Biochemistry 34, 9944-9950 (1995).
  17. Uesugi, M., Nyanguile, O., Lu, H., Levine, A. J., Verdine, G. L., Induced alpha-helix in the VP16 activation domain upon binding to a human TAF Science 277, 1310-1313 (1997).
  18. Nyanguile, O., Uesugi, M., Austin, D. J., Verdine, G. L., A non-natural transcriptional coactivator Proc. Natl. Acad. Sci. USA 94, 13402-13406 (1997).
  19. Uesugi, M., Verdine, G. L., The alpha-helical FXXphiphi motif in p53: TAF interaction and discrimination by MDM2 Proc. Natl. Acad. Sci. USA 96, 14801-14806 (1999).
  20. Park S. J., Uesugi, M., Sun, L. J., Crabtree, G. R., Verdine, G. L., Existence of a second calcineurin binding site on select isoforms of NFAT FASEB Journal, 13, A1495-A1495 (1999).
  21. Park, S., Uesugi, M., Verdine, G. L., A second calcineurin binding site on the NFAT regulatory domain Proc. Natl. Acad. Sci. USA 97, 7130-7135 (2000).
  22. Choi, Y., Asada, S., Uesugi, M.,, Divergent hTAF(II)31-binding motifs hidden in activation domains J. Biol. Chem. 275, 15912-15916 (2000).
  23. Skowyra, D., Zeremski, M., Neznanov, N., Li, M., Choi, Y., Uesugi, M., Hauser, C. A., Gu, W., Gudkov, A. V., Qin, J., Differential association of products of alternative transcripts of the candidate tumor suppressor ING1 with the mSin3/HDAC1 transcriptional corepressor complex J. Biol. Chem. 276, 8713-8719 (2001).
  24. Jabbur J. R., Tabor, A. D., Cheng, X., Wang, H., Uesugi, M., Lozano, G., Zhang, W., Phosphorylation at threonine 18 of p53 alters hydrogen bonding attenuating mdm2 binding and TAFII31 recruitment Oncogene 21, 7100-7113 (2002).
  25. Asada, S., Choi, Y., Yamada, M., Wang, S., Hung, M., Qin, J., Uesugi, M., External control of Her2 expression and cancer cell growth by targeting a Ras-linked coactivator Proc. Natl. Acad. Sci. USA 99, 12747-12752 (2002).
  26. Choi, Y., Kawazoe, Y., Murakami, K., Misawa, H., Uesugi, M., Identification of bioactive molecules by adipogenesis profiling of organic compounds J. Biol. Chem. 278, 7320-7324 (2003).
  27. Asada, S., Choi, Y., Uesugi, M., A gene-expression inhibitor that targets an alpha-helix-mediated protein interaction J. Am. Chem. Soc. 125, 4992-4993 (2003).
  28. Choi, Y., Kawazoe, Y., Murakami, K., Uesugi, M., Identification of bioactive molecules by adipogenesis profiling of organic compounds FASEB Journal, 17, A605-A605 (2003).
  29. Shimogawa, H., Kwon, Y., Mao, Q., Kawazoe, Y., Choi, Y., Asada, S., Kigoshi, H., Uesugi, M., A wrench-shaped synthetic molecule that modulates a transcription factor-coactivator interaction J. Am. Chem. Soc. 126, 3461-3471 (2004).
  30. Kawazoe, Y., Tanaka, H., Uesugi, M., Chemical genetic identification of histamine receptor H1 as a stimulator of insulin-induced adipogenesis Chem. Biol. 11, 907-913 (2004).
  31. Choi, Y., Uesugi, M., Regulation of IGF2 functions by a bioactive small molecule FASEB Journal, 18, C219-C219 (2004).
  32. Kwon, Y., Arndt, H., Mao, Q., Choi, Y., Kawazoe, Y., Dervan, P. B., Uesugi, M., Small molecule transcription factor mimic J. Am. Chem. Soc. 126, 15940-15941 (2004).
  33. Uesugi, M., Synthetic molecules that modulate transcription and differentiation: hints for future drug discovery Journal of Combinatorial Chemistry and High-Throughput Screening 7, 653-659 (2004).
  34. Choi Y, Shimogawa H, Murakami K, Ramdas L, Zhang W, Qin J, Uesugi M, Chemical Genetic Identification of the IGF-linked Pathway That is Mediated by STAT6 and MFP2 Chemistry & Biology 13, 241-249 (2006).
  35. Jung D, Choi Y, Uesugi M, Small Organic Molecules that Modulate Gene Transcription Drug Discov Today 11, 452-457 (2006).
  36. Uesugi M, Chemical Biology of Gene Expression Peptide Science 2006 , 151 (2006).
  37. Henderson YC, Frederick MJ, Jayakumar A, Choi Y, Wang MT, Kang Y, Evans R, Spring PM, Uesugi M, Clayman GL, Human LBP-32/MGR is a repressor of the P450scc in human choriocarcinoma cell line JEG-3. Placenta 28(2-3),152-160 (2006).
  38. Sato S, Kwon Y, Kamisuki S, Srivastava N, Mao Q, Kawazoe Y, Uesugi M, Polyproline-rod Approach to Isolatiing Protein Targets of Bioactive Small Molecules:Isolation of a New Target of Indomethacin J. Am. Chem. Soc. 129(4),873-880 (2007).
  39. Jung D, Shimogawa H, Kwon Y, Mao Q, Sato S, Kamisuki S, Kigoshi H, Uesugi M, Wrenchnolol Derivative Optimized for Gene Activation in Cells J. Am. Chem. Soc. 131(13),4774-4782 (2009).
  40. Yamazoe S, Shimogawa H, Sato S, Esko JD, Uesugi M, A Dumbbell-Shaped Small Molecule that Promotes Cell Adhesion and Growth Chem. Biol. 16(7),773-782 (2009).
  41. Kamisuki S, Mao Q, Abu-Elheiga L, Gu Z, Kugimiya A, Kwon Y, Shinohara T, Kawazoe Y, Sato S, Asakura K, Choo H, Sakai J, Wakil SJ, Uesugi M, A Small Molecule that Blocks Fat Synthesis by Inhibiting the Activation of SREBP Chem. Biol. 16(8),882-892 (2009).
  42. Hoshino M, Tsujimoto T, Yamazoe S, Uesugi M, Terada S. , Adhesamine, a New Synthetic Molecule, Accelerates Differentiation and Prolongs Survival of Primary-Cultured Mouse Hippocampal Neurons. Biochem. J. 427(2), 297-304 (2010).
  43. Sato S, Murata A, Shirakawa T, Uesugi M., Biochemical Target Isolation for Novices: Affinity-Based Strategies Chem. Biol. 17(6), 616-623 (2010).
  44. Sato, S.; Murata, A.; Orihara, T.; Shirakawa, T.; Suenaga, K.; Kigoshi, H.; Uesugi, M., Marine Natural Product Aurilide Activates the OPA1-Mediated Apoptosis by Binding to Prohibitin Chem. Biol. 18(1), 131-139 (2011).
  45. Shirakawa, T.; Kawazoe, Y.; Tsujikawa, T.; Jung, D.; Sato, S.; Uesugi, M., Deactivation of STAT6 through Serine 707 Phosphorylation by JNK J. Biol. Chem. 286(5), 4003-4010 (2011).
  46. Sumiya, E., Shimogawa, H., Sasaki, H., Tsutsumi, M., Yoshita, K., Ojika, M., Suenaga, K., Uesugi, M. , Cell-Morphology Profiling of a Natural Product Library Identifies Bisebromoamide and Miuraenamide A as Actin-Filament Stabilizers ACS Chem. Biol. 6(5), 425-31 (2011).
  47. Kawazoe, Y.; Shimogawa, H.; Sato, A.; Uesugi, M., A Mitochondrial Surface-Specific Fluorescent Probe Activated by Bioconversion Angew. Chem. Int. Ed. 50(24), 5478-81 (2011).
  48. Murata, A., Sato, S., Kawazoe, Y., Uesugi, M. , Small-Molecule Fluorescent Probes for Specific RNA Targets Chem. Commun. 47(16), 4712-4714 (2011).
  49. Murakami, G.; Inoue, H.; Tsukita, K.; Asai, Y.; Amagai, Y.; Aiba, K.; Shimogawa, H.; Uesugi, M.; Nakatsuji, N.; Takahashi, R. , Chemical Library Screening Identifies a Small Molecule that Downregulates SOD1 Transcription for Drugs to Treat Amyotrophic Lateral Sclerosis J Biomol Screen. 16(4), 405-14 (2011).
  50. Khambu, B.; Uesugi, M.; Kawazoe, Y. , Translational Repression Stabilizes Messenger RNA of Autophagy-Related Genes Genes Cells 16(8), 857-867 (2011).
  51. Kamisuki, S.; Shirakawa, T.; Kugimiya, A.; Abu-Elheiga, L.; Choo, H.; Yamada, K.; Shimogawa, H.; Wakil, SJ.; Uesugi, M. , Synthesis and Evaluation of Diarylthiazole Derivatives That Inhibit Activation of Sterol Regulatory Element-Binding Proteins J. Med. Chem. 54(13), 4923-4927 (2011).
  52. 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., A Small Molecule That Promotes Cardiac Differentiation of Human Pluripotent Stem Cells under Defined Cytokine- and Xeno-free Conditions. Cell Reports 2(5), 1448-1460 (2012)
  53. Jung, D.; Abu-Elheiga, L.; Ayuzawa, R.; Gu, Z.; Shirakawa, T.; Fujiki, Y.; Nakatsuji, N.; Wakil, S.J.; Uesugi, M. , Mis-localization and Inhibition of ACC1 by a Synthetic Small Molecule Biochem J. 448(3), 409-416 (2012).

Update: Mar 01,2013