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Citation
Scaramuzzino, C., Casci, I., Parodi, S., Lievens, P.M., Polanco, M.J., Milioto, C., Chivet, M., Monaghan, J., Mishra, A., Badders, N., Aggarwal, T., Grunseich, C., Sambataro, F., Basso, M., Fackelmayer, F.O., Taylor, J.P., Pandey, U.B., Pennuto, M. (2015). Protein arginine methyltransferase 6 enhances polyglutamine-expanded androgen receptor function and toxicity in spinal and bulbar muscular atrophy.  Neuron 85(1): 88--100.
FlyBase ID
FBrf0228260
Publication Type
Research paper
Abstract

Polyglutamine expansion in androgen receptor (AR) is responsible for spinobulbar muscular atrophy (SBMA) that leads to selective loss of lower motor neurons. Using SBMA as a model, we explored the relationship between protein structure/function and neurodegeneration in polyglutamine diseases. We show here that protein arginine methyltransferase 6 (PRMT6) is a specific co-activator of normal and mutant AR and that the interaction of PRMT6 with AR is significantly enhanced in the AR mutant. AR and PRMT6 interaction occurs through the PRMT6 steroid receptor interaction motif, LXXLL, and the AR activating function 2 surface. AR transactivation requires PRMT6 catalytic activity and involves methylation of arginine residues at Akt consensus site motifs, which is mutually exclusive with serine phosphorylation by Akt. The enhanced interaction of PRMT6 and mutant AR leads to neurodegeneration in cell and fly models of SBMA. These findings demonstrate a direct role of arginine methylation in polyglutamine disease pathogenesis.

PubMed ID
PubMed Central ID
PMC4305189 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Neuron
    Title
    Neuron
    Publication Year
    1988-
    ISBN/ISSN
    0896-6273
    Data From Reference
    Alleles (8)
    Genes (5)
    Human Disease Models (1)
    Natural transposons (1)
    Experimental Tools (1)
    Transgenic Constructs (8)