title: Altered splicing in exon 8 of the DNA replication factor CIZ1 affects subnuclear distribution and is associated with Alzheimer's disease.
abstract: In order to understand the gene-mediated processes underlying sporadic Alzheimer's disease (AD), we carried out a subtractive cloning screen for novel AD candidate genes. We identified the gene encoding the DNA replication factor CIZ1 (CDKN1A interacting zinc finger protein 1) as being more highly expressed in Alzheimer tissue than in healthy brains. We show here that an isoform of CIZ1 which lacks a glutamine-rich region, due to alternative splicing in exon 8, is upregulated in AD brains relative to the full-length CIZ1 protein. We demonstrate for the first time that a minimal 28 amino acid sequence within this region is required for CIZ1 to associate with the nuclear matrix and to form nuclear foci.
authors.affiliation: Eucaryotic Cell Biology Research Group, Department of Science, Roskilde University, Roskilde, Denmark.
authors.forename: Christina Mackeprang
authors.initials: CM
authors.lastname: Dahmcke
authors.forename: Stine
authors.initials: S
authors.lastname: Büchmann-Møller
authors.forename: Niels A
authors.initials: NA
authors.lastname: Jensen
authors.forename: Cathy
authors.initials: C
authors.lastname: Mitchelmore
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D004261:DNA Replication / Q000502:physiology*; D005091:Exons / Q000235:genetics*; D005973:Glutamine / Q000235:genetics; D006801:Humans; D042581:Intranuclear Space / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D012474:Salmon
chemical_list: C400423:Ciz1 protein, human; D009687:Nuclear Proteins; D020033:Protein Isoforms; D005973:Glutamine