例如:"lncRNA", "apoptosis", "WRKY"

4E-BP is a target of the GCN2-ATF4 pathway during Drosophila development and aging.

J. Cell Biol.2017 Jan 02;216(1):115-129. Epub 2016 Dec 15
Min-Ji Kang 1 , Deepika Vasudevan 2 , Kwonyoon Kang 1 , Kyunggon Kim 3 , Jung-Eun Park 1 , Nan Zhang 2 , Xiaomei Zeng 2 , Thomas A Neubert 4 , Michael T Marr 5 , Hyung Don Ryoo 6
Min-Ji Kang 1 , Deepika Vasudevan 2 , Kwonyoon Kang 1 , Kyunggon Kim 3 , Jung-Eun Park 1 , Nan Zhang 2 , Xiaomei Zeng 2 , Thomas A Neubert 4 , Michael T Marr 5 , Hyung Don Ryoo 6
+ et al

[No authors listed]

Author information
  • 1 Department of Biomedical Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
  • 2 Department of Cell Biology, New York University School of Medicine, New York, NY 10016.
  • 3 Proteomics Core Laboratory, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
  • 4 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.
  • 5 Department of Biology, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02453.
  • 6 Department of Cell Biology, New York University School of Medicine, New York, NY 10016 mjkang@amc.seoul.kr hyungdon.ryoo@nyumc.org.

摘要


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.