Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 387, Issue 3, Pages 476-481Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.07.062
Keywords
MHC class I chain related molecule (MIC); Tumor shedding; Protein disulfide isomerase ERp5; NKG2D; Tumor immunity; Cancer therapeutic target
Categories
Funding
- DOD-USMRC New Investigators Award [W81XWH-04-1-0577]
- DOD-USMRC IDEA Development Award [W81XWH-06-1-0014]
- NW Prostate SPORE Program
- NIH Research Grant
- NIH Temin Award [1K01CA116002]
Ask authors/readers for more resources
Expression of the MHC class I chain related molecules A and B (MICA/B) on tumor cell surface can signal the immune receptor NKG2D for tumor immune destruction. However, MIC was found to be shed by tumors in cancer patients, which negatively regulates host immunity and promotes tumor immune evasion and progression. The mechanisms by which tumors shed MIC are not well understood although diverse groups of enzymes are suggested to be involved. The functional complexity of these enzymes makes them unfeasible therapeutic targets for inhibiting MIC shedding. Here we identified an six-amino acid (6-aa) motif in the alpha 3 domain of MIC that is critical for the interaction of MIC with ERp5 to enable shedding. Mutations in this motif prevented MIC shedding but did not interfere with NKG2D-mediated recognition of MIC. Our study suggests that the 6-aa motif is a feasible target to inhibit MIC shedding for cancer therapy. (C) 2009 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available