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Genome-Wide CRISPR/Cas9-Based Screening for Deubiquitinase Subfamily Identifies Ubiquitin-Specific Protease 11 as a Novel Regulator of Osteogenic Differentiation

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dc.contributor.author정한성-
dc.contributor.author김은정-
dc.date.accessioned2022-03-11T06:04:28Z-
dc.date.available2022-03-11T06:04:28Z-
dc.date.issued2022-01-
dc.identifier.issn1661-6596-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/187927-
dc.description.abstractThe osteoblast differentiation capacity of mesenchymal stem cells must be tightly regulated, as inadequate bone mineralization can lead to osteoporosis, and excess bone formation can cause the heterotopic ossification of soft tissues. The balanced protein level of Msh homeobox 1 (MSX1) is critical during normal osteogenesis. To understand the factors that prevent MSX1 protein degradation, the identification of deubiquitinating enzymes (DUBs) for MSX1 is essential. In this study, we performed loss-of-function-based screening for DUBs regulating MSX1 protein levels using the CRISPR/Cas9 system. We identified ubiquitin-specific protease 11 (USP11) as a protein regulator of MSX1 and further demonstrated that USP11 interacts and prevents MSX1 protein degradation by its deubiquitinating activity. Overexpression of USP11 enhanced the expression of several osteogenic transcriptional factors in human mesenchymal stem cells (hMSCs). Additionally, differentiation studies revealed reduced calcification and alkaline phosphatase activity in USP11-depleted cells, while overexpression of USP11 enhanced the differentiation potential of hMSCs. These results indicate the novel role of USP11 during osteogenic differentiation and suggest USP11 as a potential target for bone regeneration.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES-
dc.publisherINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES-
dc.relation.isPartOfINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHCRISPR-Cas Systems*-
dc.subject.MESHCell Differentiation / genetics*-
dc.subject.MESHDeubiquitinating Enzymes / genetics*-
dc.subject.MESHDeubiquitinating Enzymes / metabolism-
dc.subject.MESHGene Expression Regulation-
dc.subject.MESHGenome-Wide Association Study / methods*-
dc.subject.MESHHumans-
dc.subject.MESHMSX1 Transcription Factor / genetics-
dc.subject.MESHMSX1 Transcription Factor / metabolism-
dc.subject.MESHMesenchymal Stem Cells / cytology-
dc.subject.MESHMesenchymal Stem Cells / metabolism-
dc.subject.MESHOsteogenesis / genetics*-
dc.subject.MESHProteolysis-
dc.subject.MESHRegenerative Medicine-
dc.subject.MESHThiolester Hydrolases / genetics*-
dc.subject.MESHThiolester Hydrolases / metabolism-
dc.subject.MESHTranscription Factors / metabolism-
dc.subject.MESHUbiquitination-
dc.titleGenome-Wide CRISPR/Cas9-Based Screening for Deubiquitinase Subfamily Identifies Ubiquitin-Specific Protease 11 as a Novel Regulator of Osteogenic Differentiation-
dc.typeArticle-
dc.contributor.collegeCollege of Dentistry (치과대학)-
dc.contributor.departmentDept. of Oral Biology (구강생물학교실)-
dc.contributor.googleauthorKamini Kaushal-
dc.contributor.googleauthorApoorvi Tyagi-
dc.contributor.googleauthorJanardhan Keshav Karapurkar-
dc.contributor.googleauthorEun-Jung Kim-
dc.contributor.googleauthorParthasaradhireddy Tanguturi-
dc.contributor.googleauthorKye-Seong Kim-
dc.contributor.googleauthorHan-Sung Jung-
dc.contributor.googleauthorSuresh Ramakrishna-
dc.identifier.doi10.3390/ijms23020856-
dc.contributor.localIdA03758-
dc.relation.journalcodeJ01133-
dc.identifier.eissn1422-0067-
dc.identifier.pmid35055037-
dc.subject.keywordprotein degradation-
dc.subject.keywordregenerative medicine-
dc.subject.keywordstem cells-
dc.subject.keywordubiquitination-
dc.contributor.alternativeNameJung, Han Sung-
dc.contributor.affiliatedAuthor정한성-
dc.citation.volume23-
dc.citation.number2-
dc.citation.startPage856-
dc.identifier.bibliographicCitationINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.23(2) : 856, 2022-01-
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers

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