title: RAE-1 ligands for the NKG2D receptor are regulated by E2F transcription factors, which control cell cycle entry.
abstract: The NKG2D stimulatory receptor expressed by natural killer cells and T cell subsets recognizes cell surface ligands that are induced on transformed and infected cells and facilitate immune rejection of tumor cells. We demonstrate that expression of retinoic acid early inducible gene 1 (RAE-1) family NKG2D ligands in cancer cell lines and proliferating normal cells is coupled directly to cell cycle regulation. Raet1 genes are directly transcriptionally activated by E2F family transcription factors, which play a central role in regulating cell cycle entry. Induction of RAE-1 occurred in primary cell cultures, embryonic brain cells in vivo, and cells in healing skin wounds and, accordingly, wound healing was delayed in mice lacking NKG2D. Transcriptional activation by E2Fs is likely coordinated with posttranscriptional regulation by other stress responses. These findings suggest that cellular proliferation, as occurs in cancer cells but also other pathological conditions, is a key signal tied to immune reactions mediated by NKG2D-bearing lymphocytes.
authors.affiliation: Department of Molecular and Cell Biology, 489 Life Sciences Addition, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Heiyoun
authors.initials: H
authors.lastname: Jung
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hsiung
authors.forename: Kathleen
authors.initials: K
authors.lastname: Pestal
authors.forename: Emily
authors.initials: E
authors.lastname: Procyk
authors.forename: David H
authors.initials: DH
authors.lastname: Raulet
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000276:immunology / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D050684:E2F Transcription Factors / Q000378:metabolism*; D015870:Gene Expression; D008024:Ligands; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D014158:Transcription, Genetic; D014945:Wound Healing / Q000235:genetics / Q000276:immunology / Q000502:physiology
chemical_list: D050684:E2F Transcription Factors; C527086:Klrk1 protein, mouse; D008024:Ligands; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; C491219:Raet1a protein, mouse