Abstract
Expansion of the polyglutamine repeat region of the androgen receptor (AR) results in Kennedy's disease, a neurological disorder typified by degeneration of motor neurons in the brain stem and spinal cord. As the AR has been shown to inhibit beta-catenin dependent (Wnt) signalling we asked if expansion of the polyglutamine repeats might affect this property of the protein. Using the TOPflash/FOPflash reporter assay we found that a pathogenic form of the AR containing 51 glutamine repeats showed a consistent, though minimal, reduction in its ability to inhibit beta-catenin-mediated transcription, in comparison to a non-pathogenic form with 20 repeats. A reduced ability to inhibit Wnt signalling may thus contribute in part to the underlying aetiology of Kennedy's disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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Cytoskeletal Proteins / metabolism*
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DNA Repeat Expansion*
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DNA-Binding Proteins / metabolism*
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Genes, Reporter
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Humans
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Kidney / cytology
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Lymphoid Enhancer-Binding Factor 1
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Muscular Atrophy, Spinal / genetics*
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Muscular Atrophy, Spinal / physiopathology
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Nerve Degeneration / genetics
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Nerve Degeneration / physiopathology
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Peptides / genetics
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Proto-Oncogene Proteins / metabolism
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Receptors, Androgen / genetics*
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Receptors, Androgen / metabolism*
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Signal Transduction / physiology
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Trans-Activators / metabolism*
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Transcription Factors / metabolism*
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Transcription, Genetic / physiology
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Wnt Proteins
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Zebrafish Proteins*
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beta Catenin
Substances
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CTNNB1 protein, human
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Lymphoid Enhancer-Binding Factor 1
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Peptides
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Proto-Oncogene Proteins
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Receptors, Androgen
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Trans-Activators
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Transcription Factors
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Wnt Proteins
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Zebrafish Proteins
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beta Catenin
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polyglutamine