title: Role of runt-related transcription factor 3 (RUNX3) in transcription regulation of natural cytotoxicity receptor 1 (NCR1/NKp46), an activating natural killer (NK) cell receptor.
abstract: Natural cytotoxicity receptor 1 (NCR1), also known as NKp46, is a natural killer (NK) lymphocyte-activating receptor. It is involved in major aspects of NK immune function and shows a high degree of lineage specificity in blood and bone marrow. The nature of its NK-restricted expression is not well understood. In this study, we confirm that human NCR1 NK-specific expression is achieved at the mRNA level. We found two key cis-regulatory elements in the immediate vicinity upstream of the gene. One element acts as an essential promoter, whereas the other acts as a tissue-dependent enhancer/repressor. This latter regulatory element contains a runt related-transcription factor (RUNX) recognition motif that preferentially binds RUNX3. Interfering with RUNX proteins using a dominant negative form results in decreased Ncr1 expression. RUNX3 overexpression had the opposite effect. These findings shed light on the role of RUNX3 in the control of an important NK-activating receptor.
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency and Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V5Z1L3, Canada.
authors.forename: C Benjamin
authors.initials: CB
authors.lastname: Lai
authors.forename: Dixie L
authors.initials: DL
authors.lastname: Mager
mesh_terms: D000818:Animals; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000096:biosynthesis* / Q000235:genetics; D009928:Organ Specificity / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D020218:Response Elements / Q000502:physiology*
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D012333:RNA, Messenger; C493729:Runx3 protein, human