DC Field | Value | Language |
---|---|---|
dc.contributor.author | Y D Yoo | - |
dc.contributor.author | S R Mun | - |
dc.contributor.author | C H Ji | - |
dc.contributor.author | K W Sung | - |
dc.contributor.author | K Y Kang | - |
dc.contributor.author | A J Heo | - |
dc.contributor.author | S H Lee | - |
dc.contributor.author | J Y An | - |
dc.contributor.author | Joonsung Hwang | - |
dc.contributor.author | X Q Xie | - |
dc.contributor.author | A Ciechanover | - |
dc.contributor.author | Bo Yeon Kim | - |
dc.contributor.author | Y T Kwon | - |
dc.date.accessioned | 2018-04-19T05:19:15Z | - |
dc.date.available | 2018-04-19T05:19:15Z | - |
dc.date.issued | 2018 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | 10.1073/pnas.1719110115 | ko |
dc.identifier.uri | https://oak.kribb.re.kr/handle/201005/17798 | - |
dc.description.abstract | The conjugation of amino acids to the protein N termini is universally observed in eukaryotes and prokaryotes, yet its functions remain poorly understood. In eukaryotes, the amino acid L-arginine (L-Arg) is conjugated to N-terminal Asp (Nt-Asp), Glu, Gln, Asn, and Cys, directly or associated with posttranslational modifications. Following Ntarginylation, the Nt-Arg is recognized by UBR boxes of N-recognins such as UBR1, UBR2, UBR4/p600, and UBR5/EDD, leading to substrate ubiquitination and proteasomal degradation via the N-end rule pathway. It has been a mystery, however, why studies for the past five decades identified only a handful of Nt-arginylated substrates in mammals, although five of 20 principal amino acids are eligible for arginylation. Here, we show that the Nt-Arg functions as a bimodal degron that directs substrates to either the ubiquitin (Ub)- proteasome system (UPS) or macroautophagy depending on physiological states. In normal conditions, the arginylated forms of proteolytic cleavage products, D101-CDC6 and D1156-BRCA1, are targeted to UBR box-containing N-recognins and degraded by the proteasome. However, when proteostasis by the UPS is perturbed, their Nt-Arg redirects these otherwise cellularwastes tomacroautophagy through its binding to the ZZ domain of the autophagic adaptor p62/STQSM/ Sequestosome-1. Upon binding to the Nt-Arg, p62 acts as an autophagic N-recognin that undergoes self-polymerization, facilitating cargo collection and lysosomal degradation of p62-cargo complexes. A chemical mimic of Nt-Arg redirects Ub-conjugated substrates from the UPS to macroautophagy and promotes their lysosomal degradation. Our results suggest that the Nt-Arg proteome of arginylated proteins contributes to reprogramming global proteolytic flux under stresses | - |
dc.publisher | Natl Acad Sciences | - |
dc.title | N-terminal arginylation generates a bimodal degron that modulates autophagic proteolysis | - |
dc.title.alternative | N-terminal arginylation generates a bimodal degron that modulates autophagic proteolysis | - |
dc.type | Article | - |
dc.citation.title | Proceedings of National Academy of Sciences of United States of America | - |
dc.citation.number | 12 | - |
dc.citation.endPage | e2724 | - |
dc.citation.startPage | e2716 | - |
dc.citation.volume | 115 | - |
dc.contributor.affiliatedAuthor | Joonsung Hwang | - |
dc.contributor.affiliatedAuthor | Bo Yeon Kim | - |
dc.contributor.alternativeName | 유영동 | - |
dc.contributor.alternativeName | 문수란 | - |
dc.contributor.alternativeName | 지창훈 | - |
dc.contributor.alternativeName | 성기운 | - |
dc.contributor.alternativeName | 강금영 | - |
dc.contributor.alternativeName | 허아정 | - |
dc.contributor.alternativeName | 이수현 | - |
dc.contributor.alternativeName | 안지영 | - |
dc.contributor.alternativeName | 황준성 | - |
dc.contributor.alternativeName | Xie | - |
dc.contributor.alternativeName | Ciechanover | - |
dc.contributor.alternativeName | 김보연 | - |
dc.contributor.alternativeName | 권용태 | - |
dc.identifier.bibliographicCitation | Proceedings of National Academy of Sciences of United States of America, vol. 115, no. 12, pp. e2716-e2724 | - |
dc.identifier.doi | 10.1073/pnas.1719110115 | - |
dc.subject.keyword | ATE1 R-transferase | - |
dc.subject.keyword | N-end rule pathway | - |
dc.subject.keyword | macroautophagy | - |
dc.subject.keyword | p62/STQSM/Sequestosome-1 | - |
dc.subject.keyword | ubiquitin-proteasome system | - |
dc.subject.local | ATE1 R-transferase | - |
dc.subject.local | N-end rule pathway | - |
dc.subject.local | macroautophagy | - |
dc.subject.local | Macroautophagy | - |
dc.subject.local | p62/STQSM/Sequestosome-1 | - |
dc.subject.local | ubiquitin-proteasome system | - |
dc.subject.local | Ubiquitin-proteasome system | - |
dc.description.journalClass | Y | - |
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