Amino-terminal arginylation targets endoplasmic reticulum chaperone BiP for autophagy through p62 binding.
Amino-terminal arginylation targets endoplasmic reticulum chaperone BiP for autophagy through p62 binding.
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DOI：
10.1038/ncb3177
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发表时间：
2015-07
影响因子：
21.3
通讯作者：
Kwon, Yong Tae
中科院分区：
文献类型：
--
作者：
Cha-Molstad, Hyunjoo;Sung, Ki Sa;Hwang, Joonsung;Kim, Kyoung A.;Yu, Ji Eun;Yoo, Young Dong;Jang, Jun Min;Han, Dong Hoon;Molstad, Michael;Kim, Jung Gi;Lee, Yoon Jee;Zakrzewska, Adriana;Kim, Su-Hyeon;Kim, Sung Tae;Kim, Sun Yong;Lee, Hee Gu;Soung, Nak Kyun;Ahn, Jong Seog;Ciechanover, Aaron;Kim, Bo Yeon;Kwon, Yong Tae
我们表明，ATE 1编码的精氨酸转移RNA转移酶（R-转移酶）的N-末端规则途径介导的N-末端乙酰化的多个内质网（ER）驻留伴侣，导致其胞质重定位和营业额。BiP（也称为GRP 78）、蛋白质二硫化物异构酶和钙网蛋白的N-末端双磷酸化在对细胞溶质外源DNA或蛋白酶体抑制的先天免疫应答期间与自噬共诱导，与增加的泛素化相关。精氨酸化BiP（R-BiP）由预定用于p62（也称为隔离体1，SQSTM 1）体的胞质错误折叠蛋白诱导并与其相关。R-BiP通过其N-末端精氨酸与p62 ZZ结构域的相互作用结合自噬衔接子p62。这在变构上诱导p62的自身寡聚化和聚集，并增加p62与LC 3的相互作用，导致p62靶向自噬体和R-BiP和p62连同相关货物的选择性溶酶体共降解。在这种自噬机制中，NT-精氨酸作为递送决定子、降解决定子和活化配体发挥作用。生物信息学分析预测，许多ER居民使用乙酰化来调节非ER过程。
We show thatATE1-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.
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影响因子：
64.5
作者：
Brodsky JL
通讯作者：
Brodsky JL
DOI：
10.1073/pnas.0910267107
发表时间：
2010-02-02
影响因子：
11.1
作者：
An, Jee Young;Kim, Eun-A.;Kwon, Yong Tae
通讯作者：
Kwon, Yong Tae
影响因子：
19
作者：
Kaushik S;Cuervo AM
通讯作者：
Cuervo AM
影响因子：
56.9
作者：
BACHMAIR, A;FINLEY, D;VARSHAVSKY, A
通讯作者：
VARSHAVSKY, A
影响因子：
16
作者：
Filimonenko M;Isakson P;Finley KD;Anderson M;Jeong H;Melia TJ;Bartlett BJ;Myers KM;Birkeland HC;Lamark T;Krainc D;Brech A;Stenmark H;Simonsen A;Yamamoto A
通讯作者：
Yamamoto A