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C/EBPβ参与在有丝分裂原刺激下调节p53基因的转录。

C/EBPbeta participates in regulating transcription of the p53 gene in response to mitogen stimulation.

作者信息

Boggs Kristy, Reisman David

机构信息

Department of Biological Sciences, University of South Carolina, Columbia, South Carolina 29208, USA.

出版信息

J Biol Chem. 2007 Mar 16;282(11):7982-90. doi: 10.1074/jbc.M611675200. Epub 2007 Jan 22.

Abstract

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.

摘要

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。

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