Boggs Kristy, Reisman David
Department of Biological Sciences, University of South Carolina, Columbia, South Carolina 29208, USA.
J Biol Chem. 2007 Mar 16;282(11):7982-90. doi: 10.1074/jbc.M611675200. Epub 2007 Jan 22.
The tightly regulated expression of p53 contributes to genomic stability, and transcription of the p53 gene is induced prior to cells entering S phase, possibly as a mechanism to ensure a rapid p53 response in the event of DNA damage. We have previously described the cloning of an additional 1000 bp of upstream p53 sequences that we have demonstrated play a role in the regulated expression of p53. As described in an earlier report, we preliminarily identified that a member of the CAAT/enhancer-binding protein (C/EPB) family of transcription factors may play a role in regulating p53. Here we have demonstrated that a particular C/EBPbeta isoform, C/EBPbeta-2, efficiently binds to the p53 promoter and induces its expression in a fashion that reflects the pattern of p53 expression seen as cells are induced to enter S phase and is absent from cells that are defective in proper p53 regulation. We conclude from these findings that C/EBPbeta-2 plays a central role in the regulating of p53 transcription during the transition into S phase.
p53的严格调控表达有助于基因组稳定性,并且p53基因的转录在细胞进入S期之前被诱导,这可能是一种在DNA损伤情况下确保p53快速反应的机制。我们之前描述了另外1000 bp的p53上游序列的克隆,我们已经证明这些序列在p53的调控表达中发挥作用。如早期报告所述,我们初步确定转录因子CAAT/增强子结合蛋白(C/EPB)家族的一个成员可能在调节p53中发挥作用。在这里,我们已经证明一种特定的C/EBPβ异构体,即C/EBPβ-2,能够有效地结合到p53启动子上,并以一种反映细胞被诱导进入S期时p53表达模式的方式诱导其表达,而在p53调控缺陷的细胞中则不存在这种表达模式。我们从这些发现中得出结论,C/EBPβ-2在进入S期的转变过程中对p53转录的调节起着核心作用。