Cited 25 times in
Autophagy is induced by raptor degradation via the ubiquitin/proteasome system in granular corneal dystrophy type 2
DC Field | Value | Language |
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dc.contributor.author | 맹용선 | - |
dc.contributor.author | 최승일 | - |
dc.contributor.author | 김응권 | - |
dc.contributor.author | 김태임 | - |
dc.date.accessioned | 2015-12-28T11:04:19Z | - |
dc.date.available | 2015-12-28T11:04:19Z | - |
dc.date.issued | 2014 | - |
dc.identifier.issn | 0006-291X | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/138631 | - |
dc.description.abstract | Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant disorder that is caused by a point mutation in transforming growth factor-β-induced gene-h3 (TGFBI), which encodes transforming growth factor-β-induced protein (TGFBIp). Recently, we found that the autophagic clearance of mutant-TGFBIp is delayed in GCD2 corneal fibroblasts; however, any potential correlation between mutant-TGFBIp turnover and autophagy-lysosome pathway remains unknown. Here, we report that mutant-TGFBIp is accumulated and that autophagy, a key clearance pathway for mutant-TGFBIp, is induced in primary cultured GCD2 homozygous (HO) and wild-type (WT) corneal fibroblasts that express exogenously introduced mutant-TGFBIp. Mutant-TGFBI colocalized with LC3-enriched cytosolic vesicles and cathepsin D in primary cultured GCD2 corneal fibroblasts. We also observed reduced levels of raptor (regulatory-associated protein of the mammalian target of rapamycin [mTOR]) in GCD2 corneal fibroblasts and WT corneal fibroblasts expressing mutant-TGFBIp. Strikingly, treatment with MG132, a ubiquitin/proteasome system inhibitor, significantly increased the levels of both total and ubiquitinated raptor in GCD2 corneal fibroblasts. The levels of the autophagy marker LC3-II were also increased in WT corneal fibroblasts that were treated with shRNA against raptor. However, mutant-TGFBIp accumulated in autophagosomes or/and lysosomes in spite of the significant activation of basal autophagy in GCD2 corneal fibroblasts. These results suggest that an insufficient autophagy-lysosome pathway might be responsible for the intracellular accumulation of mutant-TGFBIp during the pathogenesis of GCD2 | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 1505~1511 | - |
dc.relation.isPartOf | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Adaptor Proteins, Signal Transducing/metabolism* | - |
dc.subject.MESH | Autophagy* | - |
dc.subject.MESH | Corneal Dystrophies, Hereditary/enzymology | - |
dc.subject.MESH | Corneal Dystrophies, Hereditary/metabolism* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Proteasome Endopeptidase Complex/metabolism* | - |
dc.subject.MESH | Proteolysis | - |
dc.subject.MESH | Regulatory-Associated Protein of mTOR | - |
dc.subject.MESH | Ubiquitin/metabolism* | - |
dc.title | Autophagy is induced by raptor degradation via the ubiquitin/proteasome system in granular corneal dystrophy type 2 | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Ophthalmology (안과학) | - |
dc.contributor.googleauthor | Seung-il Choi | - |
dc.contributor.googleauthor | Yong-Sun Maeng | - |
dc.contributor.googleauthor | Kyu Seo Kim | - |
dc.contributor.googleauthor | Tae-im Kim | - |
dc.contributor.googleauthor | Eung Kweon Kim | - |
dc.identifier.doi | 10.1016/j.bbrc.2014.07.035 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A01346 | - |
dc.contributor.localId | A04099 | - |
dc.contributor.localId | A00831 | - |
dc.contributor.localId | A01080 | - |
dc.relation.journalcode | J00281 | - |
dc.identifier.eissn | 1090-2104 | - |
dc.identifier.pmid | 25044116 | - |
dc.identifier.url | http://www.sciencedirect.com/science/article/pii/S0006291X14012492 | - |
dc.subject.keyword | Autophagy | - |
dc.subject.keyword | Granular corneal dystrophy type 2 | - |
dc.subject.keyword | Raptor | - |
dc.subject.keyword | TGFBIp | - |
dc.subject.keyword | Ubiquitin/proteasome system | - |
dc.subject.keyword | mTOR | - |
dc.contributor.alternativeName | Maeng, Yong Sun | - |
dc.contributor.alternativeName | Choi, Seung Il | - |
dc.contributor.alternativeName | Kim, Eung Kweon | - |
dc.contributor.alternativeName | Kim, Tae Im | - |
dc.contributor.affiliatedAuthor | Maeng, Yong Sun | - |
dc.contributor.affiliatedAuthor | Choi, Seung Il | - |
dc.contributor.affiliatedAuthor | Kim, Eung Kweon | - |
dc.contributor.affiliatedAuthor | Kim, Tae Im | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 450 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 1505 | - |
dc.citation.endPage | 1511 | - |
dc.identifier.bibliographicCitation | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.450(4) : 1505-1511, 2014 | - |
dc.identifier.rimsid | 38455 | - |
dc.type.rims | ART | - |
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