{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Song Z"],"funding":["U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)","American Society of Nephrology","NIDDK NIH HHS","NHLBI NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)","U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","NCI NIH HHS","U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)","U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development","U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases"],"pagination":["9244"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11512042"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["Impaired secretion of an essential blood coagulation factor fibrinogen leads to hepatic fibrinogen storage disease (HFSD), characterized by the presence of fibrinogen-positive inclusion bodies and hypofibrinogenemia. However, the molecular mechanisms underlying the biogenesis of fibrinogen in the endoplasmic reticulum (ER) remain unexplored. Here we uncover a key role of SEL1L-HRD1 complex of ER-associated degradation (ERAD) in the formation of aberrant inclusion bodies, and the biogenesis of nascent fibrinogen protein complex in hepatocytes. Acute or chronic deficiency of SEL1L-HRD1 ERAD in the hepatocytes leads to the formation of hepatocellular inclusion bodies. Proteomics studies followed by biochemical assays reveal fibrinogen as a major component of the inclusion bodies. Mechanistica"],"journal":["Nature communications"],"pubmed_title":["Regulation of hepatic inclusions and fibrinogen biogenesis by SEL1L-HRD1 ERAD."],"pmcid":["PMC11512042"],"funding_grant_id":["DK090313","R01 HL168009","R01DK128077","R01 DK090313","R01DK132068","R01DK126908","R21HD104904","R01HL166382","R01HL163516","R01 DK126908","U01 CA274304"],"pubmed_authors":["Thepsuwan P","Zheng Z","Torres M","Zhang K","Fang D","Kastrup CJ","Wei X","Tushi NJ","Paton JC","Wu SA","Paton AW","Jaiman S","Hur WS","Flick MJ","Ferraresso F","Sun S","Wei J","Song Z"],"additional_accession":[]},"is_claimable":false,"name":"Regulation of hepatic inclusions and fibrinogen biogenesis by SEL1L-HRD1 ERAD.","description":"Impaired secretion of an essential blood coagulation factor fibrinogen leads to hepatic fibrinogen storage disease (HFSD), characterized by the presence of fibrinogen-positive inclusion bodies and hypofibrinogenemia. However, the molecular mechanisms underlying the biogenesis of fibrinogen in the endoplasmic reticulum (ER) remain unexplored. Here we uncover a key role of SEL1L-HRD1 complex of ER-associated degradation (ERAD) in the formation of aberrant inclusion bodies, and the biogenesis of nascent fibrinogen protein complex in hepatocytes. Acute or chronic deficiency of SEL1L-HRD1 ERAD in the hepatocytes leads to the formation of hepatocellular inclusion bodies. Proteomics studies followed by biochemical assays reveal fibrinogen as a major component of the inclusion bodies. Mechanistica","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2026-06-02T23:27:40.721Z","creation":"2025-04-06T03:14:00.943Z"},"accession":"S-EPMC11512042","cross_references":{"pubmed":["39455574"],"doi":["10.1038/s41467-024-53639-x"]}}