Autophagy Regulates Homeostasis of Pluripotency-Associated Proteins in hESCs

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dc.contributor.authorCho, Yun-Heeko
dc.contributor.authorHan, Kyu Minko
dc.contributor.authorKim, Dong Kyuko
dc.contributor.authorLee, Joonsunko
dc.contributor.authorLee, Sang Heeko
dc.contributor.authorChoi, Kyeng-Wonko
dc.contributor.authorKim, Junghoko
dc.contributor.authorHan, Yong Mahnko
dc.date.accessioned2014-09-04T08:19:45Z-
dc.date.available2014-09-04T08:19:45Z-
dc.date.created2013-11-11-
dc.date.created2013-11-11-
dc.date.issued2014-02-
dc.identifier.citationSTEM CELLS, v.32, no.2, pp.424 - 435-
dc.identifier.issn1066-5099-
dc.identifier.urihttp://hdl.handle.net/10203/189944-
dc.description.abstractThe pluripotency of embryonic stem cells (ESCs) is maintained by intracellular networks of many pluripotency-associated (PA) proteins such as OCT4, SOX2, and NANOG. However, the mechanisms underlying the regulation of protein homeostasis for pluripotency remain elusive. Here, we first demonstrate that autophagy acts together with the ubiquitin-proteasome system (UPS) to modulate the levels of PA proteins in human ESCs (hESCs). Autophagy inhibition impaired the pluripotency despite increment of PA proteins in hESCs. Immunogold-electron microscopy confirmed localization of OCT4 molecules within autophagosomes. Also, knockdown of LC3 expression led to accumulation of PA proteins and reduction of pluripotency in hESCs. Interestingly, autophagy and the UPS showed differential kinetics in the degradation of PA proteins. Autophagy inhibition caused enhanced accumulation of both cytoplasmic and nuclear PA proteins, whereas the UPS inhibition led to preferentially degrade nuclear PA proteins. Our findings suggest that autophagy modulates homeostasis of PA proteins, providing a new insight in the regulation of pluripotency in hESCs. Stem Cells2014;32:424-435-
dc.languageEnglish-
dc.publisherWILEY-BLACKWELL-
dc.subjectEMBRYONIC STEM-CELLS-
dc.subjectUBIQUITIN-PROTEASOME SYSTEM-
dc.subjectSELF-RENEWAL-
dc.subjectES CELLS-
dc.subjectOCT4-
dc.subjectDIFFERENTIATION-
dc.subjectTRANSCRIPTION-
dc.subjectDEGRADATION-
dc.subjectDISEASE-
dc.subjectLINES-
dc.titleAutophagy Regulates Homeostasis of Pluripotency-Associated Proteins in hESCs-
dc.typeArticle-
dc.identifier.wosid000330742100009-
dc.identifier.scopusid2-s2.0-84894601452-
dc.type.rimsART-
dc.citation.volume32-
dc.citation.issue2-
dc.citation.beginningpage424-
dc.citation.endingpage435-
dc.citation.publicationnameSTEM CELLS-
dc.identifier.doi10.1002/stem.1589-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.contributor.localauthorHan, Yong Mahn-
dc.contributor.nonIdAuthorChoi, Kyeng-Won-
dc.contributor.nonIdAuthorKim, Jungho-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorEmbryonic stem cells-
dc.subject.keywordAuthorPluripotency-
dc.subject.keywordAuthorCell culture-
dc.subject.keywordAuthorCell signaling-
dc.subject.keywordPlusEMBRYONIC STEM-CELLS-
dc.subject.keywordPlusUBIQUITIN-PROTEASOME SYSTEM-
dc.subject.keywordPlusSELF-RENEWAL-
dc.subject.keywordPlusES CELLS-
dc.subject.keywordPlusOCT4-
dc.subject.keywordPlusDIFFERENTIATION-
dc.subject.keywordPlusTRANSCRIPTION-
dc.subject.keywordPlusDEGRADATION-
dc.subject.keywordPlusDISEASE-
dc.subject.keywordPlusLINES-
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