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4E-BP is a target of the GCN2-ATF4 pathway during Drosophila development and aging.
Kang, Min-Ji; Vasudevan, Deepika; Kang, Kwonyoon; Kim, Kyunggon; Park, Jung-Eun; Zhang, Nan; Zeng, Xiaomei; Neubert, Thomas A; Marr, Michael T; Ryoo, Hyung Don.
Afiliación
  • Kang MJ; Department of Cell Biology, New York University School of Medicine, New York, NY 10016 mjkang@amc.seoul.kr hyungdon.ryoo@nyumc.org.
  • Vasudevan D; Department of Biomedical Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
  • Kang K; Department of Cell Biology, New York University School of Medicine, New York, NY 10016.
  • Kim K; Department of Biomedical Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
  • Park JE; Proteomics Core Laboratory, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
  • Zhang N; Department of Biomedical Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
  • Zeng X; Department of Cell Biology, New York University School of Medicine, New York, NY 10016.
  • Neubert TA; Department of Cell Biology, New York University School of Medicine, New York, NY 10016.
  • Marr MT; Department of Biochemistry and Molecular Pharmacology, Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016.
  • Ryoo HD; Department of Biology, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02453.
J Cell Biol ; 216(1): 115-129, 2017 01 02.
Article en En | MEDLINE | ID: mdl-27979906
Reduced amino acid availability attenuates mRNA translation in cells and helps to extend lifespan in model organisms. The amino acid deprivation-activated kinase GCN2 mediates this response in part by phosphorylating eIF2α. In addition, the cap-dependent translational inhibitor 4E-BP is transcriptionally induced to extend lifespan in Drosophila melanogaster, but through an unclear mechanism. Here, we show that GCN2 and its downstream transcription factor, ATF4, mediate 4E-BP induction, and GCN2 is required for lifespan extension in response to dietary restriction of amino acids. The 4E-BP intron contains ATF4-binding sites that not only respond to stress but also show inherent ATF4 activity during normal development. Analysis of the newly synthesized proteome through metabolic labeling combined with click chemistry shows that certain stress-responsive proteins are resistant to inhibition by 4E-BP, and gcn2 mutant flies have reduced levels of stress-responsive protein synthesis. These results indicate that GCN2 and ATF4 are important regulators of 4E-BP transcription during normal development and aging.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Quinasas / Factores de Transcripción / Envejecimiento / Factores de Iniciación de Péptidos / Proteínas de Drosophila / Péptidos y Proteínas de Señalización Intracelular / Drosophila melanogaster / Factor de Transcripción Activador 4 Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Cell Biol Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Quinasas / Factores de Transcripción / Envejecimiento / Factores de Iniciación de Péptidos / Proteínas de Drosophila / Péptidos y Proteínas de Señalización Intracelular / Drosophila melanogaster / Factor de Transcripción Activador 4 Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Cell Biol Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos