Sugars K L, Budhram-Mahadeo V, Packham G, Latchman D S
Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
Nucleic Acids Res. 2001 Nov 15;29(22):4530-40. doi: 10.1093/nar/29.22.4530.
The Brn-3a transcription factor stimulates the expression of the anti-apoptotic Bcl-2 and Bcl-x proteins and protects neuronal cells from apoptosis. Here we show that a minimal Bcl-x promoter is activated by Brn-3a and that this stimulation is prevented by the pro-apoptotic p53 protein. Both these effects are mediated via Bcl-x promoter sequences, which are indistinguishable from those required for minimal basal promoter activity. A newly described upstream Bcl-x promoter is also activated by Brn-3a with this activation being prevented by p53. Hence, Brn-3a-mediated activation of two distinct Bcl-x promoters and of the Bcl-2 promoter is blocked by p53 whereas this is not observed for Brn-3a activated promoters derived from genes not involved in inhibiting apoptosis. p53 therefore appears to specifically target the activation by Brn-3a of promoters derived from genes with an anti-apoptotic effect and this may be involved in the pro-apoptotic activity of p53.
Brn-3a转录因子可刺激抗凋亡蛋白Bcl-2和Bcl-x的表达，保护神经元细胞免于凋亡。在此我们表明，最小的Bcl-x启动子可被Brn-3a激活，而这种刺激可被促凋亡蛋白p53阻断。这两种效应均通过Bcl-x启动子序列介导，这些序列与最小基础启动子活性所需的序列并无差异。新描述的上游Bcl-x启动子也可被Brn-3a激活，且这种激活可被p53阻断。因此，p53可阻断Brn-3a介导的两个不同Bcl-x启动子及Bcl-2启动子的激活，而对于Brn-3a激活的源自不参与抑制凋亡的基因的启动子则未观察到这种情况。因此，p53似乎特异性靶向Brn-3a对具有抗凋亡作用基因的启动子的激活，这可能与p53的促凋亡活性有关。
