title: LANP mediates neuritic pathology in Spinocerebellar ataxia type 1.
abstract: Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disease that results from a pathogenic glutamine-repeat expansion in the protein ataxin-1 (ATXN1). Although the functions of ATXN1 are still largely unknown, there is evidence to suggest that ATXN1 plays a role in regulating gene expression, the earliest process known to go awry in SCA1 mouse models. In this study, we show that ATXN1 reduces histone acetylation, a post-translational modification of histones associated with enhanced transcription, and represses histone acetyl transferase-mediated transcription. In addition, we find that depleting the Leucine-rich Acidic Nuclear Protein (LANP)-an ATXN1 binding inhibitor of histone acetylation-reverses aspects of SCA1 neuritic pathology.
authors.affiliation: Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Marija
authors.initials: M
authors.lastname: Cvetanovic
authors.forename: Rupinder K
authors.initials: RK
authors.lastname: Kular
authors.forename: Puneet
authors.initials: P
authors.lastname: Opal
mesh_terms: D000107:Acetylation; D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D005786:Gene Expression Regulation / Q000502:physiology; D055879:Gene Knock-In Techniques; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000096:biosynthesis*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism*; D016716:PC12 Cells; D011499:Protein Processing, Post-Translational; D051381:Rats; D020754:Spinocerebellar Ataxias / Q000378:metabolism / Q000473:pathology
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; C000593751:Atxn1 protein, rat; D006657:Histones; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051548:Histone Acetyltransferases