title: Ataxin-1 and Brother of ataxin-1 are components of the Notch signalling pathway.
abstract: Ataxin-1 (ATXN1), a causative factor for spinocerebellar ataxia type 1 (SCA1), and the related Brother of ATXN1 (BOAT1) are human proteins involved in transcriptional repression. So far, little is known about which transcriptional pathways mediate the effects of ATXN1 and BOAT1. From our analyses of the properties of BOAT1 in Drosophila and of both proteins in mammalian cells, we report here that BOAT1 and ATXN1 are components of the Notch signalling pathway. In Drosophila, BOAT1 compromises the activities of Notch. In mammalian cells, both ATXN1 and BOAT1 bind to the promoter region of Hey1 and inhibit the transcriptional output of Notch through direct interactions with CBF1, a transcription factor that is crucial for the Notch pathway. Our results suggest that, in addition to their involvement in SCA1, ATXN1 and BOAT1 might participate in several Notch-controlled developmental and pathological processes.
authors.affiliation: Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey 08854, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Tong
authors.forename: Hongxing
authors.initials: H
authors.lastname: Gui
authors.forename: Feng
authors.initials: F
authors.lastname: Jin
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Heck
authors.forename: Peihui
authors.initials: P
authors.lastname: Lin
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Fondell
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Tsai
mesh_terms: D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism; D047468:Immunoprecipitation; D051379:Mice; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering / Q000235:genetics; D051880:Receptors, Notch / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D020798:Two-Hybrid System Techniques
chemical_list: D000067696:Ataxin-1; D000067528:Ataxins; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D017931:DNA Primers; D029721:Drosophila Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D012097:Repressor Proteins; C000593749:ATXN1 protein, human; C504974:ATXN1L protein, human; C000593750:Atxn1 protein, mouse; C485631:HEY1 protein, human; C497570:RBPJ protein, human; C088731:Su(H) protein, Drosophila