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

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Item Type:	Article
Title:	Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1-PP2A protein complex
Creators Name:	Krauss, S., Griesche, N., Jastrzebska, E., Chen, C., Rutschow, D., Achmüller, C., Dorn, S., Boesch, S.M., Lalowski, M., Wanker, E., 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
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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