{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["19(15)"],"submitter":["Yang X"],"pubmed_abstract":["Spondyloepiphyseal dysplasia (SEMD) is a rare disease in which cartilage growth is disrupted, and the DDRGK1 mutation is one of the causative genes. In our study, we established <i>Ddrgk1</i><sup>fl/fl</sup>, <i>Col2a1</i>-ERT Cre mice, which showed a thickened hypertrophic zone (HZ) in the growth plate, simulating the previous reported SEMD pathology <i>in vivo</i>. Instead of the classical modulation mechanism towards SOX9, our further mechanism study found that DDRGK1 stabilizes the stress sensor endoplasmic reticulum-to-nucleus signaling 1 (IRE1α) to maintain endoplasmic reticulum (ER) homoeostasis. The loss of DDRGK1 decreased the UFMylation and subsequently led to increased ubiquitylation-mediated IRE1α degradation, causing ER dysfunction and activating the PERK/CHOP/Caspase3 apoptos"],"journal":["International journal of biological sciences"],"pagination":["4709-4725"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10539710"],"repository":["biostudies-literature"],"pubmed_title":["Loss of DDRGK1 impairs IRE1α UFMylation in spondyloepiphyseal dysplasia."],"pmcid":["PMC10539710"],"pubmed_authors":["Yang X","Xia Y","Ma P","Qin A","Cao X","Cao Y","Ma H","Zhou T","Wang X","Cheng X","Zhao J"],"additional_accession":[]},"is_claimable":false,"name":"Loss of DDRGK1 impairs IRE1α UFMylation in spondyloepiphyseal dysplasia.","description":"Spondyloepiphyseal dysplasia (SEMD) is a rare disease in which cartilage growth is disrupted, and the DDRGK1 mutation is one of the causative genes. In our study, we established <i>Ddrgk1</i><sup>fl/fl</sup>, <i>Col2a1</i>-ERT Cre mice, which showed a thickened hypertrophic zone (HZ) in the growth plate, simulating the previous reported SEMD pathology <i>in vivo</i>. Instead of the classical modulation mechanism towards SOX9, our further mechanism study found that DDRGK1 stabilizes the stress sensor endoplasmic reticulum-to-nucleus signaling 1 (IRE1α) to maintain endoplasmic reticulum (ER) homoeostasis. The loss of DDRGK1 decreased the UFMylation and subsequently led to increased ubiquitylation-mediated IRE1α degradation, causing ER dysfunction and activating the PERK/CHOP/Caspase3 apoptos","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023","modification":"2025-04-22T16:01:12.6Z","creation":"2025-02-19T01:45:54.609Z"},"accession":"S-EPMC10539710","cross_references":{"pubmed":["37781516"],"doi":["10.7150/ijbs.82765"]}}