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Updated: Jun 25, 2026
11:19
Novel RNA-Binding Proteins Isolation by the RaPID Methodology
Published on: September 30, 2016
Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G
Robert A Eagle1, Gillian Flack, Anthony Warford
1Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrookes Hospital, Cambridge, UK. robeagle@caltech.edu
Plos One
|February 19, 2009
Summary
Two ULBP5/RAET1G variants have distinct functions. RAET1G1 is intracellular in tumors, while soluble RAET1G2 may help tumors evade Natural Killer (NK) cell immunity.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- The activating immunoreceptor NKG2D is crucial for anti-tumor and anti-viral immunity.
- NKG2D ligands, including MIC and ULBP/RAET families, are upregulated on diseased cells.
- Two splicing variants of ULBP5/RAET1G exist but lack extensive characterization.
Purpose of the Study:
- To characterize the expression, trafficking, and function of the two ULBP5/RAET1G isoforms.
- To investigate the role of ULBP5/RAET1G in cancer and immune responses.
Main Methods:
- Analysis of ULBP5/RAET1G transcripts in cancer cell lines and primary tumors.
- Immunohistochemical staining of tissue microarrays using anti-RAET1G1 antiserum.
- Investigation of protein localization (intracellular vs. cell surface) and secretion.
- Assessment of RAET1G2's effect on NKG2D receptor expression on NK cells.
Main Results:
- Both ULBP5/RAET1G transcripts are frequently expressed in epithelial cancers and primary breast cancers.
- RAET1G1 expression is restricted in normal tissues but increased in celiac disease and various tumors.
- RAET1G1 is primarily intracellular, with limited cell surface expression.
- RAET1G2 is a secreted molecule that downregulates NKG2D on NK cells, suggesting a tumor immune evasion mechanism.
Conclusions:
- ULBP5/RAET1G isoforms exhibit distinct cellular localizations, implying unique functions.
- Expression patterns of ULBP5/RAET1G are similar to the NKG2D ligand MICA.
- Secreted RAET1G2 represents a potential novel strategy for tumor immune evasion.
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