Calnan B J, Szychowski S, Chan F K, Cado D, Winoto A
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA.
Immunity. 1995 Sep;3(3):273-82. doi: 10.1016/1074-7613(95)90113-2.
The transcription factor Nur77, an orphan member of the nuclear hormone receptor superfamily, is highly expressed during T cell receptor-signaled apoptosis, suggesting a possible role for Nur77 in negative selection. We examined this by generating two sets of transgenic mice. In one set of mice, a dominant-negative Nur77 mutant is constitutively expressed and the other in which wild-type Nur77 protein is constitutively expressed in developing thymocytes. We report that inhibition of endogenous Nur77 by the dominant-negative mutant perturbed T cell development and inhibited antigen-induced negative selection in F5T cell receptor transgenic mice. Constitutive expression of wild-type Nur77 protein induced apoptosis in developing thymocytes, resulting in a decreased number of thymocytes and mature T cells. Together, these data support a role for Nur77 in the downstream signaling events in antigen-induced negative selection.
转录因子Nur77是核激素受体超家族的一个孤儿成员，在T细胞受体信号传导诱导的凋亡过程中高表达，提示Nur77在阴性选择中可能发挥作用。我们通过构建两组转基因小鼠对此进行了研究。在一组小鼠中，组成性表达显性负性Nur77突变体，另一组中，在发育中的胸腺细胞中组成性表达野生型Nur77蛋白。我们报告，显性负性突变体对内源性Nur77的抑制扰乱了T细胞发育，并抑制了F5 T细胞受体转基因小鼠中抗原诱导的阴性选择。野生型Nur77蛋白的组成性表达诱导发育中的胸腺细胞凋亡，导致胸腺细胞和成熟T细胞数量减少。总之，这些数据支持Nur77在抗原诱导的阴性选择的下游信号事件中发挥作用。
