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Amino-terminal arginylation as a degradation signal for selective autophagy
Amino-terminal arginylation as a degradation signal for selective autophagy
BMB Reports. 2015. Sep, 48(9): 487-488
Copyright © 2015, Korean Society for Biochemistry and Molecular Biology
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • Received : August 24, 2015
  • Published : September 30, 2015
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About the Authors
Hyunjoo Cha-Molstad
World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Cheongwon 28116, Korea
Yong Tae Kwon
Protein Metabolism Medical Research Center and Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul 03080, Korea
yok5@snu.ac.kr
Bo Yeon Kim
World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Cheongwon 28116, Korea
yok5@snu.ac.kr

Abstract
The ubiquitin-proteasome system and the autophagy lysosome system are the two major protein degradation machineries in eukaryotic cells. These two systems coordinate the removal of unwanted intracellular materials, but the mechanism by which they achieve this synchronization is largely unknown. The ubiquitination of substrates serves as a universal degradation signal for both systems. Our study revealed that the amino-terminal Arg, a canonical N-degron in the ubiquitin-proteasome system, also acts as a degradation signal in autophagy. We showed that many ER residents, such as BiP, contain evolutionally conserved arginylation permissive pro-N-degrons, and that certain inducers like dsDNA or proteasome inhibitors cause their translocation into the cytoplasm where they bind misfolded proteins and undergo amino-terminal arginylation by arginyl transferase 1 (ATE1). The amino-terminal Arg of BiP binds p62, which triggers p62 oligomerization and enhances p62-LC3 interaction, thereby stimulating autophagic delivery and degradation of misfolded proteins, promoting cell survival. This study reveals a novel ubiquitin-independent mechanism for the selective autophagy pathway, and provides an insight into how these two major protein degradation pathways communicate in cells to dispose the unwanted proteins. [BMB Reports 2015; 48(9): 487-488]
Keywords
ATE1p62Autophagy
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Acknowledgements
This work was supported by the World Class Institute (WCI) Program (WCI 2009-002 to B.Y.K.), the Bio and Medical Technology Development Program (NRF-2014M3A9B5073938 to B.Y.K.), the Basic Science Research Program (NRF-2013R1A2A2A01014170 to Y.T.K.) of the National Research Foundation (NRF) funded by the Ministry of Science, ICT and Future Planning (MSIP) of Korea, and also by the KRIBB Research Initiative Program (to B.Y.K) and NIH grant HL083365 (to Y.T.K).
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