Production of an antigenic peptide by insulin-degrading enzyme.
Nat Immunol
; 11(5): 449-54, 2010 May.
Article
em En
| MEDLINE
| ID: mdl-20364150
ABSTRACT
Most antigenic peptides presented by major histocompatibility complex (MHC) class I molecules are produced by the proteasome. Here we show that a proteasome-independent peptide derived from the human tumor protein MAGE-A3 is produced directly by insulin-degrading enzyme (IDE), a cytosolic metallopeptidase. Cytotoxic T lymphocyte recognition of tumor cells was reduced after metallopeptidase inhibition or IDE silencing. Separate inhibition of the metallopeptidase and the proteasome impaired degradation of MAGE-A3 proteins, and simultaneous inhibition of both further stabilized MAGE-A3 proteins. These results suggest that MAGE-A3 proteins are degraded along two parallel pathways that involve either the proteasome or IDE and produce different sets of antigenic peptides presented by MHC class I molecules.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Linfócitos T Citotóxicos
/
Apresentação de Antígeno
/
Insulisina
/
Antígenos de Neoplasias
/
Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article