title: Caspase-3 cleaves the expanded androgen receptor protein of spinal and bulbar muscular atrophy in a polyglutamine repeat length-dependent manner.
abstract: Spinal and bulbar muscular atrophy (SBMA) is one of a group of human inherited neurodegenerative diseases caused by polyglutamine expansion. There is increasing evidence that generation of truncated proteins containing an expanded polyglutamine tract may be an important step in the pathogenesis of these disorders. We have previously demonstrated that the SBMA gene product, the androgen receptor (AR) protein, is toxic when truncated. We now report that in vitro translated full-length AR proteins containing different sized polyglutamine repeats (24, 65 and 97 repeats, respectively) are specifically cleaved by recombinant caspase-3, liberating a polyglutamine containing fragment, and that the susceptibility to cleavage is polyglutamine repeat length-dependent. These findings suggest that AR protein is one of the "death substrates" cleaved by caspase-3 and that caspase-3 might be involved in the pathogenesis of SBMA.
authors.affiliation: Department of Neurology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: S
authors.initials: S
authors.lastname: Miwa
authors.forename: D E
authors.initials: DE
authors.lastname: Merry
authors.forename: A
authors.initials: A
authors.lastname: Kume
authors.forename: L
authors.initials: L
authors.lastname: Mei
authors.forename: M
authors.initials: M
authors.lastname: Doyu
authors.forename: G
authors.initials: G
authors.lastname: Sobue
mesh_terms: D010244:Bulbar Palsy, Progressive / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D016472:Motor Neuron Disease / Q000378:metabolism*; D009134:Muscular Atrophy, Spinal / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D014176:Protein Biosynthesis; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D004792:Enzyme Precursors; D010455:Peptides; D011944:Receptors, Androgen; D011994:Recombinant Proteins; C097188:polyglutamine; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases