title: Characterization of Aes nuclear foci in colorectal cancer cells.
abstract: Amino-terminal enhancer of split (Aes) is a member of Groucho/Transducin-like enhancer (TLE) family. Aes is a recently found metastasis suppressor of colorectal cancer (CRC) that inhibits Notch signalling, and forms nuclear foci together with TLE1. Although some Notch-associated proteins are known to form subnuclear bodies, little is known regarding the dynamics or functions of these structures. Here, we show that Aes nuclear foci in CRC observed under an electron microscope are in a rather amorphous structure, lacking surrounding membrane. Investigation of their behaviour during the cell cycle by time-lapse cinematography showed that Aes nuclear foci dissolve during mitosis and reassemble after completion of cytokinesis. We have also found that heat shock cognate 70 (HSC70) is an essential component of Aes foci. Pharmacological inhibition of the HSC70 ATPase activity with VER155008 reduces Aes focus formation. These results provide insight into the understanding of Aes-mediated inhibition of Notch signalling.
authors.affiliation: Department of Pharmacology and Department of Surgery, Graduate School of Medicine, Kyoto University, Yoshida Konoé-cho, Sakyo-ku, Kyoto 606-8501, Japan;
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Itatani
authors.affiliation: Department of Pharmacology and.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sonoshita
authors.affiliation: Department of Pharmacology and.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kakizaki
authors.affiliation: Drug Discovery Research Laboratories, Kyowa Hakko Kirin Co., Ltd, 1188 Shimotogari Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan;
authors.forename: Katsuya
authors.initials: K
authors.lastname: Okawa
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 rue University, Montreal, Quebec H3A 2B4, Canada; and.
authors.forename: Stefano
authors.initials: S
authors.lastname: Stifani
authors.affiliation: Department of Life Science, Faculty of Engineering and Resource Science, Akita University, 1-1 Tegata Gakuen Town, Akita, 010-0852 Akita, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Itoh
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Yoshida Konoé-cho, Sakyo-ku, Kyoto 606-8501, Japan;
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Department of Pharmacology and Department of Surgery, Graduate School of Medicine, Kyoto University, Yoshida Konoé-cho, Sakyo-ku, Kyoto 606-8501, Japan; taketo@mfour.med.kyoto-u.ac.jp.
authors.forename: M Mark
authors.initials: MM
authors.lastname: Taketo
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D056970:Co-Repressor Proteins; D015179:Colorectal Neoplasms / Q000378:metabolism*; D048749:Cytokinesis; D045325:HCT116 Cells; D057809:HEK293 Cells; D050883:HSC70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D008938:Mitosis; D011684:Purine Nucleosides / Q000494:pharmacology; D051880:Receptors, Notch / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D059008:Time-Lapse Imaging
chemical_list: D056970:Co-Repressor Proteins; D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D011684:Purine Nucleosides; D051880:Receptors, Notch; D012097:Repressor Proteins; C499043:TLE1 protein, human; C498445:TLE5 protein, human; C550733:VER 155008; D000251:Adenosine Triphosphatases
keywords: Notch signalling; colorectal cancer; heat shock protein; nuclear matrix; transcription