RAET1E2, a soluble isoform of the UL16-binding protein RAET1E produced by tumor cells, inhibits NKG2D-mediated NK cytotoxicity

Wei Cao, Xueyan Xi, Zhiyong Hao, Wenjing Li, Yan Kong, Lianxian Cui, Chi Ma, Denian Ba, Wei He

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

UL16-binding proteins (ULBPs, also termed as retinoic acid early transcripts, encoded by RAET1 genes), a family of ligands for NKG2D in humans, are frequently expressed by tumor cells and mediate cytotoxicities of natural killer (NK) cells and CD8+ αβ T cells to tumor cells. ULBP1, ULBP2, ULBP3, and RAET1L link to membrane through glycosylphosphatidylinositol, whereas RAET1E and RAET1G contain transmembrane and cytoplasmic domains. Proteolytic cleavage of ULBP2 produces truncated and soluble forms that may counteract NKG2D-mediated tumor immune surveillance. In this study, we report that RAET1E can produce a soluble, 35-kDa protein (termed as RAET1E2) lacking the transmembrane region by selective splicing in tumor cells. The expressions of both RAET1E2 transcripts and protein can be found in different tumor cells and tissues. Preincubation of NK-92 cells, a human NK cell line, with culture supernatants from tumor cell lines expressing RAET1E2 or RAET1E2 gene-transfected COS-7 cells resulted in decreased expression of NKG2D on NK-92 cells. Furthermore, incubation of NK-92 cells with recombinant RAET1E2 protein also decreased the surface expression of NKG2D and resulted in marked reduction in cytotoxicities to MGC-803, HepG2, or K562 tumor cells. Taken together, our data provide strong evidence for an immune escape mechanism of tumors via alternative splicing of ULBP RNA to generate a free soluble ULBP protein, RAET1E2, that may impair NKG2D-mediated NK cell cytotoxicity to tumors.

Original languageEnglish
Pages (from-to)18922-18928
Number of pages7
JournalJournal of Biological Chemistry
Volume282
Issue number26
DOIs
Publication statusPublished - 29 Jun 2007
Externally publishedYes

Fingerprint

Cytotoxicity
Tumors
Carrier Proteins
Protein Isoforms
Natural Killer Cells
Cells
Neoplasms
Tumor Escape
Glycosylphosphatidylinositols
Proteins
Genes
K562 Cells
COS Cells
Alternative Splicing
Tretinoin
Tumor Cell Line
Recombinant Proteins
T-cells
Cell culture
Ligands

ASJC Scopus subject areas

  • Biochemistry

Cite this

RAET1E2, a soluble isoform of the UL16-binding protein RAET1E produced by tumor cells, inhibits NKG2D-mediated NK cytotoxicity. / Cao, Wei; Xi, Xueyan; Hao, Zhiyong; Li, Wenjing; Kong, Yan; Cui, Lianxian; Ma, Chi; Ba, Denian; He, Wei.

In: Journal of Biological Chemistry, Vol. 282, No. 26, 29.06.2007, p. 18922-18928.

Research output: Contribution to journalArticle

Cao, Wei ; Xi, Xueyan ; Hao, Zhiyong ; Li, Wenjing ; Kong, Yan ; Cui, Lianxian ; Ma, Chi ; Ba, Denian ; He, Wei. / RAET1E2, a soluble isoform of the UL16-binding protein RAET1E produced by tumor cells, inhibits NKG2D-mediated NK cytotoxicity. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 26. pp. 18922-18928.
@article{2f2729d8c22d4f69be6c1c34809912a1,
title = "RAET1E2, a soluble isoform of the UL16-binding protein RAET1E produced by tumor cells, inhibits NKG2D-mediated NK cytotoxicity",
abstract = "UL16-binding proteins (ULBPs, also termed as retinoic acid early transcripts, encoded by RAET1 genes), a family of ligands for NKG2D in humans, are frequently expressed by tumor cells and mediate cytotoxicities of natural killer (NK) cells and CD8+ αβ T cells to tumor cells. ULBP1, ULBP2, ULBP3, and RAET1L link to membrane through glycosylphosphatidylinositol, whereas RAET1E and RAET1G contain transmembrane and cytoplasmic domains. Proteolytic cleavage of ULBP2 produces truncated and soluble forms that may counteract NKG2D-mediated tumor immune surveillance. In this study, we report that RAET1E can produce a soluble, 35-kDa protein (termed as RAET1E2) lacking the transmembrane region by selective splicing in tumor cells. The expressions of both RAET1E2 transcripts and protein can be found in different tumor cells and tissues. Preincubation of NK-92 cells, a human NK cell line, with culture supernatants from tumor cell lines expressing RAET1E2 or RAET1E2 gene-transfected COS-7 cells resulted in decreased expression of NKG2D on NK-92 cells. Furthermore, incubation of NK-92 cells with recombinant RAET1E2 protein also decreased the surface expression of NKG2D and resulted in marked reduction in cytotoxicities to MGC-803, HepG2, or K562 tumor cells. Taken together, our data provide strong evidence for an immune escape mechanism of tumors via alternative splicing of ULBP RNA to generate a free soluble ULBP protein, RAET1E2, that may impair NKG2D-mediated NK cell cytotoxicity to tumors.",
author = "Wei Cao and Xueyan Xi and Zhiyong Hao and Wenjing Li and Yan Kong and Lianxian Cui and Chi Ma and Denian Ba and Wei He",
year = "2007",
month = "6",
day = "29",
doi = "10.1074/jbc.M702504200",
language = "English",
volume = "282",
pages = "18922--18928",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "26",

}

TY - JOUR

T1 - RAET1E2, a soluble isoform of the UL16-binding protein RAET1E produced by tumor cells, inhibits NKG2D-mediated NK cytotoxicity

AU - Cao, Wei

AU - Xi, Xueyan

AU - Hao, Zhiyong

AU - Li, Wenjing

AU - Kong, Yan

AU - Cui, Lianxian

AU - Ma, Chi

AU - Ba, Denian

AU - He, Wei

PY - 2007/6/29

Y1 - 2007/6/29

N2 - UL16-binding proteins (ULBPs, also termed as retinoic acid early transcripts, encoded by RAET1 genes), a family of ligands for NKG2D in humans, are frequently expressed by tumor cells and mediate cytotoxicities of natural killer (NK) cells and CD8+ αβ T cells to tumor cells. ULBP1, ULBP2, ULBP3, and RAET1L link to membrane through glycosylphosphatidylinositol, whereas RAET1E and RAET1G contain transmembrane and cytoplasmic domains. Proteolytic cleavage of ULBP2 produces truncated and soluble forms that may counteract NKG2D-mediated tumor immune surveillance. In this study, we report that RAET1E can produce a soluble, 35-kDa protein (termed as RAET1E2) lacking the transmembrane region by selective splicing in tumor cells. The expressions of both RAET1E2 transcripts and protein can be found in different tumor cells and tissues. Preincubation of NK-92 cells, a human NK cell line, with culture supernatants from tumor cell lines expressing RAET1E2 or RAET1E2 gene-transfected COS-7 cells resulted in decreased expression of NKG2D on NK-92 cells. Furthermore, incubation of NK-92 cells with recombinant RAET1E2 protein also decreased the surface expression of NKG2D and resulted in marked reduction in cytotoxicities to MGC-803, HepG2, or K562 tumor cells. Taken together, our data provide strong evidence for an immune escape mechanism of tumors via alternative splicing of ULBP RNA to generate a free soluble ULBP protein, RAET1E2, that may impair NKG2D-mediated NK cell cytotoxicity to tumors.

AB - UL16-binding proteins (ULBPs, also termed as retinoic acid early transcripts, encoded by RAET1 genes), a family of ligands for NKG2D in humans, are frequently expressed by tumor cells and mediate cytotoxicities of natural killer (NK) cells and CD8+ αβ T cells to tumor cells. ULBP1, ULBP2, ULBP3, and RAET1L link to membrane through glycosylphosphatidylinositol, whereas RAET1E and RAET1G contain transmembrane and cytoplasmic domains. Proteolytic cleavage of ULBP2 produces truncated and soluble forms that may counteract NKG2D-mediated tumor immune surveillance. In this study, we report that RAET1E can produce a soluble, 35-kDa protein (termed as RAET1E2) lacking the transmembrane region by selective splicing in tumor cells. The expressions of both RAET1E2 transcripts and protein can be found in different tumor cells and tissues. Preincubation of NK-92 cells, a human NK cell line, with culture supernatants from tumor cell lines expressing RAET1E2 or RAET1E2 gene-transfected COS-7 cells resulted in decreased expression of NKG2D on NK-92 cells. Furthermore, incubation of NK-92 cells with recombinant RAET1E2 protein also decreased the surface expression of NKG2D and resulted in marked reduction in cytotoxicities to MGC-803, HepG2, or K562 tumor cells. Taken together, our data provide strong evidence for an immune escape mechanism of tumors via alternative splicing of ULBP RNA to generate a free soluble ULBP protein, RAET1E2, that may impair NKG2D-mediated NK cell cytotoxicity to tumors.

UR - http://www.scopus.com/inward/record.url?scp=34547132338&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547132338&partnerID=8YFLogxK

U2 - 10.1074/jbc.M702504200

DO - 10.1074/jbc.M702504200

M3 - Article

VL - 282

SP - 18922

EP - 18928

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 26

ER -