转录因子C／EBPβ的研究进展

C／EBPs增强子结合蛋白是核转录因子,其作用范围广泛,既参与正常的生理代谢过程,又与多种疾病的发生和发展相关,其作用方式多样,对转录有正、负调控作用。C／EBPβ是其第二位成员主要通过对靶细胞基因转录的调节,参与细胞的增殖与分化、肿瘤的发生与凋亡等重要生命活动;其功能受到蛋白酶降解、磷酸化、蛋白质相互作用等多种途径的调控。本文就C／EBPs的调控机理及其与肿瘤的关系综述如下。     

EBP50 exerts tumor suppressor activity by promoting cell apoptosis and retarding extracellular signal-regulated kinase activity

The expression of Ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) and the intragenic mutation of the ebp50 gene have been reported to correlate with human breast cancer development, but the exact impacts on breast cancer development and its molecular mechanism are not fully understood. In this study, we investigate the potential function of EBP50 through over-expression in the breast cancer cell line, MDA-MB-231, which has low EBP50 protein expression levels. The effects of EBP50 over-expression on cellular proliferation, anchorage-independent growth and apoptosis were examined. In addition, the activity of extracellular signal-regulated kinase (ERK) was also determined. Our results show that a decrease of cellular proliferation and attenuation of colony-forming ability were evident in MDA-MB-231 cells stably transfected with an EBP50 expressing plasmid (EBP-231) when compared with control cells. There was also a statistically significant increase in spontaneous apoptosis in EBP-231 cells accompanied by an attenuation in ERK activity. Altogether, our results suggest that restoring EBP50 expression could suppress breast cancer cell proliferation by promoting cell apoptosis and inhibiting ERK activity, and that EBP50 may be a target for development of diagnostics and therapeutics in breast cancer.     

Peroxisome proliferator-activated receptor-gamma activation inhibits interleukin-1beta -mediated platelet-derived growth factor-alpha receptor gene expression via CCAAT/enhancer-binding protein-delta in vascular smooth muscle cells

CCAAT/enhancer-binding protein (C/EBP)-binding motifs have been identified in the promoter regions of interleukin (IL)-6, tumor necrosis factor-alpha, and platelet-derived growth factor-alpha receptor (PDGFalphaR). Recently, peroxisome proliferator-activated receptors (PPARs) have been suggested to be important immunomodulatory mediators. Although many studies have demonstrated that the interaction between C/EBPs and PPARs plays a central role in lipid metabolism, expression and function of these factors are unknown in vascular smooth muscle cells (VSMCs). In the present study, we clarified a functional relationship between C/EBPs and PPARgamma in the regulation of IL-1beta-induced PDGFalphaR expression in VSMCs. PPARgamma activators, troglitazone and 15-deoxy-Delta(12,14)-prostaglandin J(2), inhibited IL-1beta-induced PDGFalphaR expression and suppressed PDGF-induced proliferation activity of VSMCs. Electromobility shift and supershift assays for a C/EBP motif in the PDGFalphaR promoter region revealed that PPARgamma activators suppressed IL-1beta-induced DNA binding activity of C/EBPdelta and beta. PPARgamma activators also suppressed IL-1beta-induced C/EBPdelta expression. In contrast, overexpression of C/EBPdelta reversed the suppressive effect of PPARgamma activators on PDGFalphaR expression almost completely. From these results, we conclude that the inhibitory effect of PPARgamma activators on PDGFalphaR expression is mainly mediated by C/EBPdelta suppression. Regulation of C/EBPdelta by PPARgamma activators probably plays critical roles in modulating inflammatory responses in the arterial wall.