title: Pathologically Relevant Prelamin A Interactions with Transcription Factors.
abstract: LMNA-linked laminopathies are a group of rare human diseases caused by mutations in LMNA or by disrupted posttranslational processing of its largest encoded isoform, prelamin A. The accumulation of mutated or immature forms of farnesylated prelamin A, named progerin or prelamin A, respectively, dominantly disrupts nuclear lamina structure with toxic effects in cells. One hypothesis is that aberrant lamin filament networks disrupt or "trap" proteins such as transcription factors, thereby interfering with their normal activity. Since laminopathies mainly affect tissues of mesenchymal origin, we tested this hypothesis by generating an experimental model of laminopathy by inducing prelamin A accumulation in human mesenchymal stem cells (hMSCs). We provide detailed protocols for inducing and detecting prelamin A accumulation in hMSCs, and describe the bioinformatic analysis and in vitro assays of transcription factors potentially affected by prelamin A accumulation.
authors.affiliation: Stem Cells and Cell Therapy Laboratory, BioCruces Health Research Institute, Cruces University Hospital, Barakaldo, Spain.
authors.forename: Arantza
authors.initials: A
authors.lastname: Infante
authors.affiliation: Stem Cells and Cell Therapy Laboratory, BioCruces Health Research Institute, Cruces University Hospital, Barakaldo, Spain. Electronic address: cirodriguez@osakidetza.eus.
authors.forename: Clara I
authors.initials: CI
authors.lastname: Rodríguez
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003198:Computer Simulation; D063990:Gene Ontology; D006801:Humans; D034904:Lamin Type A / Q000502:physiology*; D008661:Metabolism, Inborn Errors / Q000235:genetics; D008957:Models, Genetic; D058977:Molecular Sequence Annotation; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D034904:Lamin Type A; D014157:Transcription Factors; C090764:prelamin A
keywords: Human experimental models; Human mesenchymal stem cells; Laminopathies; Prelamin A; Transcription factors