{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hoffmann S"],"funding":["Kraeftens Bekaempelse (Danish Cancer Society)","Danmarks Grundforskningsfond","European Research Council","Lundbeckfonden (Lundbeck Foundation)","Kræftens Bekæmpelse","Novo Nordisk Fonden (NNF)","Novo Nordisk Foundation Center for Protein Research","Lundbeckfonden","Novo Nordisk Fonden","Lundbeck Foundation","Danmarks Grundforskningsfond (DNRF)"],"pagination":["e50662"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7534640"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["21(10)"],"pubmed_abstract":["Dominant missense mutations in the human serine protease FAM111A underlie perinatally lethal gracile bone dysplasia and Kenny-Caffey syndrome, yet how FAM111A mutations lead to disease is not known. We show that FAM111A proteolytic activity suppresses DNA replication and transcription by displacing key effectors of these processes from chromatin, triggering rapid programmed cell death by Caspase-dependent apoptosis to potently undermine cell viability. Patient-associated point mutations in FAM111A exacerbate these phenotypes by hyperactivating its intrinsic protease activity. Moreover, FAM111A forms a complex with the uncharacterized homologous serine protease FAM111B, point mutations in which cause a hereditary fibrosing poikiloderma syndrome, and we demonstrate that disease-associated FA"],"journal":["EMBO reports"],"pubmed_title":["FAM111 protease activity undermines cellular fitness and is amplified by gain-of-function mutations in human disease."],"pmcid":["PMC7534640"],"funding_grant_id":["R223-2016-281","R231-A13972","NNF18OC0054680","PI Niels Mailand","R303-2018-3212","616236","PI Matthias Mann","DNRF115","PI Nicholas MI Taylor","NNF14CC0001","R231‐A13972","NNF18OC0030752","R303‐2018-3212"],"pubmed_authors":["Mailand N","Mund A","Gallo M","Taylor NM","Hoffmann S","Pentakota S","Haahr P","Coscia F","Mann M"],"additional_accession":[]},"is_claimable":false,"name":"FAM111 protease activity undermines cellular fitness and is amplified by gain-of-function mutations in human disease.","description":"Dominant missense mutations in the human serine protease FAM111A underlie perinatally lethal gracile bone dysplasia and Kenny-Caffey syndrome, yet how FAM111A mutations lead to disease is not known. We show that FAM111A proteolytic activity suppresses DNA replication and transcription by displacing key effectors of these processes from chromatin, triggering rapid programmed cell death by Caspase-dependent apoptosis to potently undermine cell viability. Patient-associated point mutations in FAM111A exacerbate these phenotypes by hyperactivating its intrinsic protease activity. Moreover, FAM111A forms a complex with the uncharacterized homologous serine protease FAM111B, point mutations in which cause a hereditary fibrosing poikiloderma syndrome, and we demonstrate that disease-associated FA","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Oct","modification":"2026-05-05T01:13:40.886Z","creation":"2020-10-29T08:40:05Z"},"accession":"S-EPMC7534640","cross_references":{"pubmed":["32776417"],"doi":["10.15252/embr.202050662"]}}