An six-amino acid motif in the α3 domain of MICA is the cancer therapeutic target to inhibit shedding

Xuanjun Wang, Ashley D. Lundgren, Pragya Singh, David R. Goodlett, Stephen R. Plymate, Jennifer D. Wu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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 α3 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.

Original languageEnglish (US)
Pages (from-to)476-481
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume387
Issue number3
DOIs
StatePublished - Sep 25 2009

Keywords

  • Cancer therapeutic target
  • MHC class I chain related molecule (MIC)
  • NKG2D
  • Protein disulfide isomerase ERp5
  • Tumor immunity
  • Tumor shedding

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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