An six-amino acid motif in the alpha3 domain of MICA is the cancer therapeutic target to inhibit shedding.

Abstract:

: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 alpha3 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.

authors

Wang X,Lundgren AD,Singh P,Goodlett DR,Plymate SR,Wu JD

doi

10.1016/j.bbrc.2009.07.062

subject

Has Abstract

pub_date

2009-09-25 00:00:00

pages

476-81

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(09)01389-8

journal_volume

387

pub_type

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