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A RUNX2 stabilization pathway mediates physiologic and pathologic bone formation

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dc.contributor.author박광환-
dc.date.accessioned2020-09-28T11:10:31Z-
dc.date.available2020-09-28T11:10:31Z-
dc.date.issued2020-05-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/179179-
dc.description.abstractThe osteoblast differentiation capacity of skeletal stem cells (SSCs) must be tightly regulated, as inadequate bone formation results in low bone mass and skeletal fragility, and over-exuberant osteogenesis results in heterotopic ossification (HO) of soft tissues. RUNX2 is essential for tuning this balance, but the mechanisms of posttranslational control of RUNX2 remain to be fully elucidated. Here, we identify that a CK2/HAUSP pathway is a key regulator of RUNX2 stability, as Casein kinase 2 (CK2) phosphorylates RUNX2, recruiting the deubiquitinase herpesvirus-associated ubiquitin-specific protease (HAUSP), which stabilizes RUNX2 by diverting it away from ubiquitin-dependent proteasomal degradation. This pathway is important for both the commitment of SSCs to osteoprogenitors and their subsequent maturation. This CK2/HAUSP/RUNX2 pathway is also necessary for HO, as its inhibition blocked HO in multiple models. Collectively, active deubiquitination of RUNX2 is required for bone formation and this CK2/HAUSP deubiquitination pathway offers therapeutic opportunities for disorders of inappropriate mineralization.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherNature Pub. Group-
dc.relation.isPartOfNATURE COMMUNICATIONS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAdult-
dc.subject.MESHAged-
dc.subject.MESHAnimals-
dc.subject.MESHCasein Kinase II / genetics-
dc.subject.MESHCasein Kinase II / metabolism-
dc.subject.MESHCell Differentiation-
dc.subject.MESHCleidocranial Dysplasia / genetics-
dc.subject.MESHCleidocranial Dysplasia / pathology-
dc.subject.MESHCore Binding Factor Alpha 1 Subunit / metabolism*-
dc.subject.MESHFemale-
dc.subject.MESHGene Deletion-
dc.subject.MESHHaploinsufficiency / genetics-
dc.subject.MESHHindlimb / metabolism-
dc.subject.MESHHumans-
dc.subject.MESHMale-
dc.subject.MESHMice, Inbred C57BL-
dc.subject.MESHMiddle Aged-
dc.subject.MESHOssification, Heterotopic / genetics-
dc.subject.MESHOssification, Heterotopic / metabolism*-
dc.subject.MESHOssification, Heterotopic / pathology-
dc.subject.MESHOsteoblasts / metabolism-
dc.subject.MESHOsteogenesis*-
dc.subject.MESHPhosphorylation-
dc.subject.MESHProtein Stability-
dc.subject.MESHRNA, Messenger / genetics-
dc.subject.MESHRNA, Messenger / metabolism-
dc.subject.MESHUbiquitin-Specific Peptidase 7 / metabolism-
dc.titleA RUNX2 stabilization pathway mediates physiologic and pathologic bone formation-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Orthopedic Surgery (정형외과학교실)-
dc.contributor.googleauthorJung-Min Kim-
dc.contributor.googleauthorYeon-Suk Yang-
dc.contributor.googleauthorKwang Hwan Park-
dc.contributor.googleauthorXianpeng Ge-
dc.contributor.googleauthorRen Xu-
dc.contributor.googleauthorNa Li-
dc.contributor.googleauthorMinkyung Song-
dc.contributor.googleauthorHyunho Chun-
dc.contributor.googleauthorSeoyeon Bok-
dc.contributor.googleauthorJulia F Charles-
dc.contributor.googleauthorOdile Filhol-Cochet-
dc.contributor.googleauthorBrigitte Boldyreff-
dc.contributor.googleauthorTeresa Dinter-
dc.contributor.googleauthorPaul B Yu-
dc.contributor.googleauthorNing Kon-
dc.contributor.googleauthorWei Gu-
dc.contributor.googleauthorTakeshi Takarada-
dc.contributor.googleauthorMatthew B Greenblatt-
dc.contributor.googleauthorJae-Hyuck Shim-
dc.identifier.doi10.1038/s41467-020-16038-6-
dc.contributor.localIdA01437-
dc.relation.journalcodeJ02293-
dc.identifier.eissn2041-1723-
dc.identifier.pmid32385263-
dc.contributor.alternativeNamePark, Kwang Hwan-
dc.contributor.affiliatedAuthor박광환-
dc.citation.volume11-
dc.citation.number1-
dc.citation.startPage2289-
dc.identifier.bibliographicCitationNATURE COMMUNICATIONS, Vol.11(1) : 2289, 2020-05-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers

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