Terry Fox Laboratory, British Columbia Cancer Agency and Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V5Z1L3, Canada.
J Biol Chem. 2012 Mar 2;287(10):7324-34. doi: 10.1074/jbc.M111.306936. Epub 2012 Jan 17.
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.
自然细胞毒性受体 1（NCR1），也称为 NKp46，是一种自然杀伤（NK）淋巴细胞激活受体。它参与 NK 免疫功能的主要方面，并在血液和骨髓中表现出高度的谱系特异性。其 NK 限制表达的性质尚不清楚。在这项研究中，我们证实人类 NCR1 的 NK 特异性表达是在 mRNA 水平上实现的。我们在基因的上游紧邻位置发现了两个关键的顺式调控元件。一个元件作为必需的启动子，而另一个元件作为组织依赖性增强子/抑制剂。这个后者的调控元件包含一个 runt 相关转录因子（RUNX）识别基序，该基序优先与 RUNX3 结合。使用显性负形式干扰 RUNX 蛋白会导致 Ncr1 表达降低。RUNX3 的过表达则产生相反的效果。这些发现揭示了 RUNX3 在控制重要的 NK 激活受体中的作用。
