Grumont Raelene, Lock Peter, Mollinari Michael, Shannon Frances M, Moore Anna, Gerondakis Steve
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Immunity. 2004 Jul;21(1):19-30. doi: 10.1016/j.immuni.2004.06.004.
Cell growth during the G1 stage of the cell cycle is partly controlled by inducing c-myc expression, which in B cells is regulated by the NF-kappaB1 and c-Rel transcription factors. Here, we show that c-myc-dependent growth during T cell activation requires c-Rel and RelA and that blocking this growth by inhibiting protein kinase C theta (PKCtheta) coincides with a failure to upregulate c-myc due to impaired RelA nuclear import and inhibition of NFAT-dependent c-rel transcription. These results demonstrate that different Rel/NF-kappaB dimers regulate the mitogenic growth of mature T and B cells, with a signaling pathway incorporating PKCtheta and NFAT controlling c-Rel/RelA-induced c-myc expression in activated T cells.
细胞周期G1期的细胞生长部分受c-myc表达诱导的控制,在B细胞中,c-myc由NF-κB1和c-Rel转录因子调控。在此,我们表明T细胞活化过程中依赖c-myc的生长需要c-Rel和RelA,并且通过抑制蛋白激酶Cθ(PKCθ)来阻断这种生长与由于RelA核输入受损和NFAT依赖性c-rel转录受抑制而未能上调c-myc相吻合。这些结果表明,不同的Rel/NF-κB二聚体调节成熟T细胞和B细胞的促有丝分裂生长,一条包含PKCθ和NFAT的信号通路控制活化T细胞中c-Rel/RelA诱导的c-myc表达。