Stimulation of an unfolded protein response impairs MHC class I expression

• Tipo: Artigo em Revista Científica Internacional
• Data: 2007

Autores

de almeida, sf (Autor) Outra; fleming, jv (Autor) Outra; azevedo, je (Autor) ICBAS; carmo-fonseca, m (Autor) Outra; de sousa, m (Autor) Outra

Revista

Título: Journal of Immunology

Vol. 178

Páginas: 3612-3619

ISSN: 0022-1767

Editora: American Association of Immunologists

Indexação

ISI Web of Knowledge - 27 Citações

Scopus - 29 Citações

Outras Informações

ID Authenticus: P-004-B5T

Abstract (EN): HFE C282Y is an example of a mutant protein that does not fold correctly, is retained in the endoplasmic reticulum, and was found previously to diminish surface expression of MHC class I (MHC-I). We now show that its expression in 293T cells triggers an unfolded protein response (UPR), as revealed by the increased levels of H chain binding protein, GRP94, and C/EBP homologous protein. Elevated levels of these proteins were also found in HFE C282Y homozygous PBMCs. Following the UPR induction, a decrease in MHC-I cell surface expression was observed. This defect in MHC-I could be mimicked, however, by overexpression of transcriptionally active isoforms of activating transcription factor-6 and X box-binding protein-1, which induced the UPR, and reversed in HFE C282Y-expressing cells by using dominant-negative constructs that block UPR signaling. The present results provide evidence to the finding that stimulation of an UPR affects MHC-I expression.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 8