title: The subcellular localization and activity of cortactin is regulated by acetylation and interaction with Keap1.
abstract: Cortactin is an F-actin-binding protein that localizes to the cell cortex, where the actin remodeling that is required for cell migration occurs. We found that cortactin shuttled between the cytoplasm and the nucleus under basal conditions. We identified Kelch-like ECH-associated protein 1 (Keap1), a cytosolic protein that is involved in oxidant stress responses, as a binding partner of cortactin that promoted the cortical localization of cortactin and cell migration. The ability of cortactin to promote cell migration is regulated by various posttranslational modifications, including acetylation. We showed that the acetylated form of cortactin was mainly localized to the nucleus and that acetylation of cortactin decreased cell migration by inhibiting the binding of cortactin to Keap1. Our findings reveal that Keap1 regulates cell migration by affecting the subcellular localization and activity of cortactin independently of its role in oxidant stress responses.
authors.affiliation: Chemical Genetics Laboratory, RIKEN, Wako, Saitama 351-0198, Japan. Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ito
authors.affiliation: Chemical Genetics Laboratory, RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Shimazu
authors.affiliation: Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Maeda
authors.affiliation: Chemical Genetics Laboratory, RIKEN, Wako, Saitama 351-0198, Japan. Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570, Japan.
authors.forename: Asad Ali
authors.initials: AA
authors.lastname: Shah
authors.affiliation: Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan. Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.affiliation: Biomedicinal Information Research Center, The National Institute of Advanced Industrial Science and Technology, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Shun-Ichiro
authors.initials: S
authors.lastname: Iemura
authors.affiliation: Biomedicinal Information Research Center, The National Institute of Advanced Industrial Science and Technology, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Natsume
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
authors.forename: Hozumi
authors.initials: H
authors.lastname: Motohashi
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Chemical Genetics Laboratory, RIKEN, Wako, Saitama 351-0198, Japan. Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan. Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570, Japan. Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan. yoshidam@riken.jp.
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000107:Acetylation; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D051356:Cortactin / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000072019:Kelch-Like ECH-Associated Protein 1; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C495868:CTTN protein, human; D051356:Cortactin; C495869:Cttn protein, mouse; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; C117301:Keap1 protein, mouse; D000072019:Kelch-Like ECH-Associated Protein 1