PEBP1, a RAF kinase inhibitory protein, negatively regulates starvation-induced autophagy by direct interaction with LC3
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Noh, Hae Sook | - |
dc.contributor.author | Hah, Young-Sool | - |
dc.contributor.author | Zada, Sahib | - |
dc.contributor.author | Ha, Ji Hye | - |
dc.contributor.author | Sim, Gyujin | - |
dc.contributor.author | Hwang, Jin Seok | - |
dc.contributor.author | Lai, Trang Huyen | - |
dc.contributor.author | Huynh Quoc Nguyen | - |
dc.contributor.author | Park, Jae-Yong | - |
dc.contributor.author | Kim, Hyun Joon | - |
dc.contributor.author | Byun, June-Ho | - |
dc.contributor.author | Hahm, Jong Ryeal | - |
dc.contributor.author | Kang, Kee Ryeon | - |
dc.contributor.author | Kim, Deok Ryong | - |
dc.date.accessioned | 2021-09-04T05:02:10Z | - |
dc.date.available | 2021-09-04T05:02:10Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2016 | - |
dc.identifier.issn | 1554-8627 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/90159 | - |
dc.description.abstract | Autophagy plays a critical role in maintaining cell homeostasis in response to various stressors through protein conjugation and activation of lysosome-dependent degradation. MAP1LC3B/LC3B (microtubule- associated protein 1 light chain 3 ) is conjugated with phosphatidylethanolamine (PE) in the membranes and regulates initiation of autophagy through interaction with many autophagy-related proteins possessing an LC3-interacting region (LIR) motif, which is composed of 2 hydrophobic amino acids (tryptophan and leucine) separated by 2 non-conserved amino acids (WXXL). In this study, we identified a new putative LIR motif in PEBP1/RKIP (phosphatidylethanolamine binding protein 1) that was originally isolated as a PE-binding protein and also a cellular inhibitor of MAPK/ERK signaling. PEBP1 was specifically bound to PE-unconjugated LC3 in cells, and mutation (WXXL mutated to AXXA) of this LIR motif disrupted its interaction with LC3 proteins. Interestingly, overexpression of PEBP1 significantly inhibited starvation-induced autophagy by activating the AKT and MTORC1 (mechanistic target of rapamycin [serine/threonine kinase] complex 1) signaling pathway and consequently suppressing the ULK1 (unc-51 like autophagy activating kinase 1) activity. In contrast, ablation of PEBP1 expression dramatically promoted the autophagic process under starvation conditions. Furthermore, PEBP1 lacking the LIR motif highly stimulated starvation-induced autophagy through the AKT-MTORC1-dependent pathway. PEBP1 phosphorylation at Ser153 caused dissociation of LC3 from the PEBP1-LC3 complex for autophagy induction. PEBP1-dependent suppression of autophagy was not associated with the MAPK pathway. These findings suggest that PEBP1 can act as a negative mediator in autophagy through stimulation of the AKT-MTORC1 pathway and direct interaction with LC3. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | TAYLOR & FRANCIS INC | - |
dc.subject | CANCER-CELLS | - |
dc.subject | ATG12-ATG5 CONJUGATE | - |
dc.subject | SELECTIVE AUTOPHAGY | - |
dc.subject | MATURATION STEP | - |
dc.subject | CARCINOMA CELLS | - |
dc.subject | ACTIVATION | - |
dc.subject | PHOSPHORYLATION | - |
dc.subject | LIPIDATION | - |
dc.subject | CISPLATIN | - |
dc.subject | COMPLEX | - |
dc.title | PEBP1, a RAF kinase inhibitory protein, negatively regulates starvation-induced autophagy by direct interaction with LC3 | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Park, Jae-Yong | - |
dc.identifier.doi | 10.1080/15548627.2016.1219013 | - |
dc.identifier.scopusid | 2-s2.0-84988384585 | - |
dc.identifier.wosid | 000387665000016 | - |
dc.identifier.bibliographicCitation | AUTOPHAGY, v.12, no.11, pp.2183 - 2196 | - |
dc.relation.isPartOf | AUTOPHAGY | - |
dc.citation.title | AUTOPHAGY | - |
dc.citation.volume | 12 | - |
dc.citation.number | 11 | - |
dc.citation.startPage | 2183 | - |
dc.citation.endPage | 2196 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | CANCER-CELLS | - |
dc.subject.keywordPlus | ATG12-ATG5 CONJUGATE | - |
dc.subject.keywordPlus | SELECTIVE AUTOPHAGY | - |
dc.subject.keywordPlus | MATURATION STEP | - |
dc.subject.keywordPlus | CARCINOMA CELLS | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordPlus | LIPIDATION | - |
dc.subject.keywordPlus | CISPLATIN | - |
dc.subject.keywordPlus | COMPLEX | - |
dc.subject.keywordAuthor | autophagy | - |
dc.subject.keywordAuthor | ERK pathway | - |
dc.subject.keywordAuthor | LC3 | - |
dc.subject.keywordAuthor | LIR motif | - |
dc.subject.keywordAuthor | MTOR | - |
dc.subject.keywordAuthor | PEBP1 | - |
dc.subject.keywordAuthor | RKIP | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(02841) 서울특별시 성북구 안암로 14502-3290-1114
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.