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Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1-PP2A protein complex

Item Type:Article
Title:Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1-PP2A protein complex
Creators Name:Krauss, S. and Griesche, N. and Jastrzebska, E. and Chen, C. and Rutschow, D. and Achmüller, C. and Dorn, S. and Boesch, S.M. and Lalowski, M. and Wanker, E. and Schneider, R. and Schweiger, S.
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.
Keywords:HeLa Cells, Luciferases, Messenger RNA, Microtubule Proteins, Nerve Tissue Proteins, Nuclear Proteins, Nucleotide Motifs, Protein Binding, Protein Biosynthesis, Protein Phosphatase 2, TOR Serine-Threonine Kinases, Transcription Factors, Trinucleotide Repeat Expansion, Western Blotting, Animals, Mice
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group (U.K.)
Volume:4
Page Range:1511
Date:26 February 2013
Official Publication:https://doi.org/10.1038/ncomms2514
PubMed:View item in PubMed

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