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- Amino-terminal arginylation targets endoplasmic reticulum chaperone BiP for autophagy through p62 binding
- Hyunjoo Cha; K S Sung; Joonsung Hwang; Kyeong A Kim; Ji-eun Yu; Y D Yoo; J M Jang; D H Han; M Molstad; Jung Gi Kim; Y J Lee; A Zakrzewska; Su Hyeon Kim; S T Kim; S Y Kim; Hee Gu Lee; Nak Kyun Soung; Jong Seog Ahn; A Ciechanover; Bo Yeon Kim; Y T Kwon
- Bibliographic Citation
- Nature Cell Biology, vol. 17, no. 7, pp. 917-929
- Publication Year
- We show that ATE1-encoded Arg-transfer RNA transferase (R-transferase) of the N-end rule pathway mediates N-terminal arginylation of multiple endoplasmic reticulum (ER)-residing chaperones, leading to their cytosolic relocalization and turnover. N-terminal arginylation of BiP (also known as GRP78), protein disulphide isomerase and calreticulin is co-induced with autophagy during innate immune responses to cytosolic foreign DNA or proteasomal inhibition, associated with increased ubiquitylation. Arginylated BiP (R-BiP) is induced by and associated with cytosolic misfolded proteins destined for p62 (also known as sequestosome 1, SQSTM1) bodies. R-BiP binds the autophagic adaptor p62 through the interaction of its N-terminal arginine with the p62 ZZ domain. This allosterically induces self-oligomerization and aggregation of p62 and increases p62 interaction with LC3, leading to p62 targeting to autophagosomes and selective lysosomal co-degradation of R-BiP and p62 together with associated cargoes. In this autophagic mechanism, Nt-arginine functions as a delivery determinant, a degron and an activating ligand. Bioinformatics analysis predicts that many ER residents use arginylation to regulate non-ER processes.
- Springer-Nature Pub Group
- Appears in Collections:
- Ochang Branch Institute > Nucleic Acid Therapeutics Research Center > 1. Journal Articles
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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