Mechanisms regulating expression of the XXXX @entity39 factor-related light gene. Role of calcium-signaling pathway in the transcriptional control.

@entity1 @entity12136 @entity39 @entity5 @entity6769 @entity205 @entity3419 @entity141 @entity3917
@entity3917 ( @entity6769 ) is a newly identified @entity5 @entity39 factor superfamily member involved in the regulation of immune responses by control of activation, maturation, and survival of immune effector cells. Despite the immunological relevance of the @entity3917 protein, little knowledge is available as to how light gene expression is regulated. In T-lymphocytes, most @entity3917 surface expression and transcript accumulation occurs after T cell activation. In this study, we have shown that these events are blocked at the transcriptional level by @entity205 , an immuno-suppressive drug. Besides, we identified a role for @entity141 -signaling pathways and NFAT transcription factors in T cell activation-induced @entity3917 expression. To further investigate this process, we have identified, cloned, and characterized a 2.1-kilobase 5'-flanking DNA genomic fragment from the @entity1 light gene. We have shown the transcriptional activity of the herein-identified minimal 5' regulatory region of @entity1 light gene parallels the endogenous expression of light in T cells. Moreover, we demonstrated that induced @entity3917 promoter activity can be equally blocked by @entity205 treatment or dominant negative NFAT overexpression and further identified by site-directed mutagenesis and electrophoretic mobility supershift analysis of a NFAT transcription factor binding site within the @entity1 light minimal promoter. Finally, @entity3419 and @entity12136 binding sites were identified and shown to regulate light basal promoter activity. Thus, the present study establishes a molecular basis to further understand the mechanisms governing @entity1 light gene expression and, consequently, could potentially lead to novel therapeutic manipulations that control the signaling cascade, resulting in @entity3917 production in conditions characterized by immunopathologic activation of T cells.
