Rojas-Marquez C, Valle-Rios R, Lopez-Bayghen E, Ortiz-Navarrete V
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados (CINVESTAV)-IPN, Av. IPN No. 2508, Colonia San Pedro Zacatenco, México, DF, Mexico.
Laboratorio de Investigación en Inmunología y Proteómica, Hospital Infantil de México Fedérico Gómez, México, DF, Mexico.
Mol Immunol. 2015 Aug;66(2):290-8. doi: 10.1016/j.molimm.2015.03.253. Epub 2015 Apr 21.
T cell activation leads to the induction of genes that are required for appropriate immune responses. This includes CRTAM (Class-I MHC-restricted T cell associated molecule), a protein that plays a key role in T cell development, proliferation, and generating cell polarity during activation. We previously characterized the CRTAM promoter and described how AP-1 family members are important for inducing CRTAM expression upon antigenic activation. Here, we show that CRTAM is a molecular target for ZEB1 (zinc finger E-box-binding protein), a homeodomain/Zn finger transcription factor. Overexpression of ZEB1 repressed CRTAM promoter activity, as well as endogenous CRTAM levels in human T cells. ZEB1-mediated transcriptional repression was abolished when E-box-like elements in the CRTAM promoter are mutated. In summary, ZEB1 functions as a transcriptional repressor for the CRTAM gene in both non-stimulated and stimulated T cells, thereby modulating adaptive immune responses.
T细胞活化会诱导产生适当免疫反应所需的基因。这包括CRTAM（I类MHC限制性T细胞相关分子），一种在T细胞发育、增殖以及活化过程中产生细胞极性方面发挥关键作用的蛋白质。我们之前对CRTAM启动子进行了表征，并描述了AP - 1家族成员在抗原活化后诱导CRTAM表达中的重要性。在此，我们表明CRTAM是ZEB1（锌指E盒结合蛋白）的分子靶点，ZEB1是一种同源结构域/锌指转录因子。ZEB1的过表达抑制了CRTAM启动子活性以及人T细胞中的内源性CRTAM水平。当CRTAM启动子中的类E盒元件发生突变时，ZEB1介导的转录抑制作用被消除。总之，ZEB1在未刺激和刺激的T细胞中均作为CRTAM基因的转录抑制因子发挥作用，从而调节适应性免疫反应。
