title: Lack of GCN5 remarkably enhances the resistance against prolonged endoplasmic reticulum stress-induced apoptosis through up-regulation of Bcl-2 gene expression.
abstract: The endoplasmic reticulum (ER), a complex membrane structure, has important roles in all eukaryotic cells. Catastrophe of its functions would lead to ER stress that causes various diseases such as cancer, neurodegenerative diseases, diabetes and so on. Prolonged ER stress could trigger apoptosis via activation of various signal transduction pathways. To investigate physiological roles of histone acetyltransferase GCN5 in regulation of ER stress, we analyzed responses of homozygous GCN5-deficient DT40 mutants, ΔGCN5, against ER stress. GCN5-deficiency in DT40 caused drastic resistance against apoptosis induced by pharmacological ER stress agents (thapsigargin and tunicamycin). Pharmaceutical analysis using specific Bcl-2 inhibitors showed that the drastic resistance against prolonged ER stress-induced apoptosis is, in part, due to up-regulation of Bcl-2 gene expression in ΔGCN5. These data revealed that GCN5 is involved in regulation of prolonged ER stress-induced apoptosis through controlling Bcl-2 gene expression.
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki 889-1692, Japan; Division of Bacteriology, Department of Infectious Diseases Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Electronic address: masakari@med.miyazaki-u.ac.jp.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Kikuchi
authors.affiliation: Division of Bacteriology, Department of Infectious Diseases Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Department of Biochemistry, Kawasaki Medical School, 577, Matsushima, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Kuribayashi
authors.affiliation: Division of Bacteriology, Department of Infectious Diseases Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Mimuro
authors.affiliation: Laboratory Center for Proteomics Research, Graduate School of Frontier Sciences, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Imajoh-Ohmi
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Takami
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nishitoh
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002645:Chickens; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D019254:Genes, bcl-2; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D019284:Thapsigargin; D051548:Histone Acetyltransferases
keywords: Apoptosis; Bcl-2; ER stress; GCN5; Gene targeting