title: Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1-PP2A protein complex.
abstract: Expansion of CAG repeats is a common feature of various neurodegenerative disorders, including Huntington's disease. Here we show that expanded CAG repeats bind to a translation regulatory protein complex containing MID1, protein phosphatase 2A and 40S ribosomal S6 kinase. Binding of the MID1-protein phosphatase 2A protein complex increases with CAG repeat size and stimulates translation of the CAG repeat expansion containing messenger RNA in a MID1-, protein phosphatase 2A- and mammalian target of rapamycin-dependent manner. Our data indicate that pathological CAG repeat expansions upregulate protein translation leading to an overproduction of aberrant protein and suggest that the MID1-complex may serve as a therapeutic target for the treatment of CAG repeat expansion disorders.
authors: German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, 53127 Bonn, Germany. Sybille.Krauss@dzne.de
authors: Sybille
authors: S
authors: Krauss
authors: Nadine
authors: N
authors: Griesche
authors: Ewa
authors: E
authors: Jastrzebska
authors: Changwei
authors: C
authors: Chen
authors: Désiree
authors: D
authors: Rutschow
authors: Clemens
authors: C
authors: Achmüller
authors: Stephanie
authors: S
authors: Dorn
authors: Sylvia M
authors: SM
authors: Boesch
authors: Maciej
authors: M
authors: Lalowski
authors: Erich
authors: E
authors: Wanker
authors: Rainer
authors: R
authors: Schneider
authors: Susann
authors: S
authors: Schweiger
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006367:HeLa Cells; D006801:Humans; D000071058:Huntingtin Protein; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008868:Microtubule Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D059372:Nucleotide Motifs; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000235:genetics*; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D008868:Microtubule Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D008156:Luciferases; C109052:MID1 protein, human; D044767:Ubiquitin-Protein Ligases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D054648:Protein Phosphatase 2