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

Kobayashi Y,Miwa S,Merry DE,Kume A,Mei L,Doyu M,Sobue G

doi

10.1006/bbrc.1998.9624

subject

Has Abstract

pub_date

1998-11-09 00:00:00

pages

145-50

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(98)99624-3

journal_volume

252

pub_type

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