Chuvpilo Sergei, Jankevics Eriks, Tyrsin Dimitri, Akimzhanov Askar, Moroz Denis, Jha Mithilesh Kumar, Schulze-Luehrmann Jan, Santner-Nanan Brigitte, Feoktistova Elizaveta, König Thomas, Avots Andris, Schmitt Edgar, Berberich-Siebelt Friederike, Schimpl Anneliese, Serfling Edgar
Department of Molecular Pathology, Institute of Pathology, University of Wuerzburg, D97080 Wuerzburg, Germany.
Immunity. 2002 Jun;16(6):881-95. doi: 10.1016/s1074-7613(02)00329-1.
Threshold levels of individual NFAT factors appear to be critical for apoptosis induction in effector T cells. In these cells, the short isoform A of NFATc1 is induced to high levels due to the autoregulation of the NFATc1 promoter P1 by NFATs. P1 is located within a CpG island in front of exon 1, represents a DNase I hypersensitive chromatin site, and harbors several sites for binding of inducible transcription factors, including a tandemly arranged NFAT site. A second promoter, P2, before exon 2, is not controlled by NFATs and directs synthesis of the longer NFATc1/B+C isoforms. Contrary to other NFATs, NFATc1/A is unable to promote apoptosis, suggesting that NFATc1/A enhances effector functions without promoting apoptosis of effector T cells.
单个NFAT因子的阈值水平似乎对效应T细胞中的凋亡诱导至关重要。在这些细胞中,由于NFAT对NFATc1启动子P1的自动调节,NFATc1的短异构体A被诱导至高水平。P1位于外显子1前方的一个CpG岛内,代表一个DNase I超敏染色质位点,并含有几个诱导型转录因子的结合位点,包括一个串联排列的NFAT位点。第二个启动子P2在外显子2之前,不受NFAT调控,并指导较长的NFATc1/B + C异构体的合成。与其他NFAT不同,NFATc1/A无法促进凋亡,这表明NFATc1/A增强效应功能而不促进效应T细胞的凋亡。