RESUMO

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.

Assuntos

Regulação da Expressão Gênica/imunologia , Proteínas de Homeodomínio/genética , Imunoglobulinas/genética , Fatores de Transcrição/genética , Imunidade Adaptativa , Sítios de Ligação , Genes Reporter , Proteínas de Homeodomínio/imunologia , Humanos , Imunoglobulinas/imunologia , Células Jurkat , Luciferases/genética , Luciferases/metabolismo , Ativação Linfocitária , NF-kappa B/genética , NF-kappa B/imunologia , Regiões Promotoras Genéticas , Ligação Proteica , Transdução de Sinais , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/imunologia , Fatores de Transcrição/imunologia , Transcrição Gênica , Homeobox 1 de Ligação a E-box em Dedo de Zinco