Amino-terminal arginylation targets endoplasmic reticulum chaperone BiP for autophagy through p62 binding

被引：213

作者：

Cha-Molstad, Hyunjoo ^{[1
]}

Sung, Ki Sa ^{[2
,3
,4
,5
]}

Hwang, Joonsung ^{[1
]}

Kim, Kyoung A. ^{[1
]}

Yu, Ji Eun ^{[1
,6
]}

Yoo, Young Dong ^{[2
,3
]}

Jang, Jun Min ^{[7
]}

Han, Dong Hoon ^{[8
]}

Molstad, Michael ^{[2
,3
]}

Kim, Jung Gi ^{[1
]}

Lee, Yoon Jee ^{[2
,3
]}

Zakrzewska, Adriana ^{[4
,5
]}

Kim, Su-Hyeon ^{[1
]}

Kim, Sung Tae ^{[2
,3
,4
,5
]}

Kim, Sun Yong ^{[9
]}

Lee, Hee Gu ^{[10
]}

Soung, Nak Kyun ^{[1
]}

Ahn, Jong Seog ^{[11
]}

Ciechanover, Aaron ^{[2
,3
,12
,13
]}

Kim, Bo Yeon ^{[1
]}

Kwon, Yong Tae ^{[2
,3
,14
]}

机构：

[1] Korea Res Inst Biosci & Biotechnol, World Class Inst, Ochang 363883, Cheongwon, South Korea

[2] Seoul Natl Univ, Coll Med, Prot Metab Med Res Ctr, Seoul 110799, South Korea

[3] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul 110799, South Korea

[4] Univ Pittsburgh, Sch Pharm, Ctr Pharmacogenet, Pittsburgh, PA 15261 USA

[5] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA

[6] Chungbuk Natl Univ, Coll Pharm, Dept Drug Discovery & Dev, Cheonju 361736, Chungbuk, South Korea

[7] Seoul Natl Univ, World Class Univ WCU Program, Dept Mol Med & Biopharmaceut Sci, Seoul 110799, South Korea

[8] Kyung Hee Univ, Coll Appl Sci, Dept Appl Chem, Yongin 446701, South Korea

[9] Ajou Univ, Sch Med, Dept Otolaryngol, Suwon 443380, South Korea

[10] Korea Res Inst Biosci & Biotechnol, Genom Struct Res Ctr, Ochang 363883, Cheongwon, South Korea

[11] Korea Res Inst Biosci & Biotechnol, Chem Biol Res Ctr, Ochang 363883, Cheongwon, South Korea

[12] Technion Israel Inst Technol, Rappaport Fac Med, Polak Tumor & Vasc Biol Res Ctr, IL-31096 Haifa, Israel

[13] Technion Israel Inst Technol, Res Inst, IL-31096 Haifa, Israel

[14] Seoul Natl Univ, Coll Med, Ischem Hypox Dis Inst, Seoul 110799, South Korea

来源：

NATURE CELL BIOLOGY | 2015年 / 17卷 / 07期

基金：

以色列科学基金会; 新加坡国家研究基金会;

关键词：

END RULE PATHWAY; UBIQUITIN-PROTEASOME SYSTEM; UNFOLDED PROTEIN RESPONSE; MOLECULAR PRINCIPLES; MEDIATED AUTOPHAGY; CELLULAR-PROTEINS; DEGRADATION; COMPONENT; CALRETICULIN; RECEPTORS;

D O I：

10.1038/ncb3177

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页码：917 / 929

页数：13

共 49 条

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