ERP57 membrane translocation dictates the immunogenicity of tumor cell death by controlling the membrane translocation of calreticulin.

Details

Serval ID
serval:BIB_B6727AA60C37
Type
Article: article from journal or magazin.
Collection
Publications
Title
ERP57 membrane translocation dictates the immunogenicity of tumor cell death by controlling the membrane translocation of calreticulin.
Journal
Journal of immunology
Author(s)
Obeid M.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Publication state
Published
Issued date
15/08/2008
Peer-reviewed
Oui
Volume
181
Number
4
Pages
2533-2543
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Several pieces of experimental evidence indicate the following: 1) the most efficient antitumor treatments (this principle applies on both chemotherapy and radiotherapy) are those that induce immunogenic cell death and are able to trigger a specific antitumor immune response; and 2) the immunogenicity of cell death depends very closely on the plasma membrane quantity of calreticulin (CRT), an endoplasmic reticulum (ER) stress protein exposed to the cell membrane after immunogenic treatment. Nevertheless, the mechanisms implicated in CRT translocation are unknown. CRT is known to interact in the ER with ERP57, another ER stress protein. I sought to determine whether ERP57 would have any role in tumor immunogenicity. In this article I report that CRT exposure is controlled by ERP57 exposure. CRT and ERP57 are translocated together in the same molecular complex. ERP57 knockdown suppressed CRT exposure as well as phagocytosis by dendritic cells and abolished the immunogenicity in vivo. Knockdown or the absence of CRT abolishes ERP57 exposure. Administration of recombinant ERP57, unlike the administration of recombinant CRT, did not restore the immunogenicity of CRT or ERP57 small interfering RNA-transfected tumor cells. Together, these studies identify ERP57 as a key protein that controls immunogenicity by controlling CRT exposure and illustrate the ability of ERP57 to serve as a new molecular marker of immunogenicity.

Keywords
Animals, Antineoplastic Agents/administration & dosage, Apoptosis Regulatory Proteins/deficiency, Apoptosis Regulatory Proteins/genetics, Apoptosis Regulatory Proteins/metabolism, Apoptosis Regulatory Proteins/physiology, Calreticulin/metabolism, Cell Death/drug effects, Cell Death/immunology, Cell Line, Cell Line, Tumor, Cell Membrane/genetics, Cell Membrane/immunology, Cell Membrane/metabolism, Endoplasmic Reticulum/drug effects, Endoplasmic Reticulum/immunology, Endoplasmic Reticulum/metabolism, Endoplasmic Reticulum/pathology, Female, Mice, Mice, Inbred BALB C, Mice, Nude, Mitoxantrone/administration & dosage, Neoplasm Transplantation, Phagocytosis/drug effects, Phagocytosis/immunology, Protein Disulfide-Isomerases/deficiency, Protein Disulfide-Isomerases/genetics, Protein Disulfide-Isomerases/metabolism, Protein Disulfide-Isomerases/physiology, Protein Transport/drug effects, Protein Transport/immunology, RNA, Small Interfering/genetics
Pubmed
Web of science
Create date
13/09/2017 17:31
Last modification date
20/08/2019 15:24
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