Dentatorubral Pallidoluysian Atrophy (DRPLA) Protein Is Cleaved by Caspase-3 during Apoptosis

Dentatorubral pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder. It is associated with an abnormal CAG repeat expansion resulting in formation of a protein with an elongated polyglutamine stretch. However, neither the physiological roles of the DRPLA gene product nor...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 1997-11, Vol.272 (46), p.29238-29242
Main Authors: Miyashita, Toshiyuki, Okamura-Oho, Yuko, Mito, Yasuyuki, Nagafuchi, Shigeo, Yamada, Masao
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Apoptosis
Caspase 3
Caspases
Cysteine Endopeptidases - metabolism
Humans
Hydrolysis
Nerve Tissue Proteins - metabolism
Neurodegenerative Diseases - metabolism
Neurodegenerative Diseases - pathology
Peptides - metabolism
Substrate Specificity
Tumor Cells, Cultured
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Dentatorubral pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder. It is associated with an abnormal CAG repeat expansion resulting in formation of a protein with an elongated polyglutamine stretch. However, neither the physiological roles of the DRPLA gene product nor molecular mechanisms of its pathogenesis have yet been elucidated. Here we report that the DRPLA protein is cleaved at a site near the N terminus during apoptosis induced by VP-16, staurosporine, or glucocorticoid. Moreover, thein vitro translated DRPLA protein is cleaved by recombinant caspase-3, a member of the cysteine protease family, which is thought to be a main executioner of apoptosis. Using mutant DRPLA proteins, the cleavage site was identified as 106DSLDG110. The cleavage, however, was not modulated by the length of the polyglutamine stretch. These findings suggest that the DRPLA protein is one of the physiological substrates of caspase-3, and its cleavage may result in structural and biochemical alterations associated with apoptosis.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.272.46.29238