Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
IUBMB Life. 2018 Jan;70(1):50-59. doi: 10.1002/iub.1698. Epub 2017 Dec 1.
The CacyBP/SIP protein is expressed at a particularly high level in brain, spleen, and various tumors. In this work, we have studied transcriptional regulation of the CacyBP/SIP gene and the influence of increased CacyBP/SIP level on gene expression in colorectal cancer HCT116 cells. We have shown that E2F1, EGR1, and CREB transcription factors bind to the CacyBP/SIP gene promoter and stimulate transcription of CacyBP/SIP gene. The role of CREB was further confirmed by the observation that forskolin, a strong activator of CREB phosphorylation/activity, increased CacyBP/SIP gene promoter activity. Moreover, we have shown that CREB dominant negative mutants, CREB133 and KCREB, inhibits CacyBP/SIP promoter activity. To check the biological significance of increased CacyBP/SIP expression/level we have applied RNA microarray analysis and have found that upregulation of CacyBP/SIP entails changes in mRNA level of many genes involved, among others, in immune processes. © 2017 IUBMB Life, 70(1):50-59, 2018.
CacyBP/SIP 蛋白在大脑、脾脏和各种肿瘤中表达水平特别高。在这项工作中，我们研究了 CacyBP/SIP 基因的转录调控以及 CacyBP/SIP 水平升高对结直肠癌细胞 HCT116 基因表达的影响。我们已经表明，E2F1、EGR1 和 CREB 转录因子结合到 CacyBP/SIP 基因启动子上，并刺激 CacyBP/SIP 基因的转录。通过观察发现， forskolin 是 CREB 磷酸化/活性的强激活剂，增加了 CacyBP/SIP 基因启动子的活性，进一步证实了 CREB 的作用。此外，我们已经表明，CREB 显性负突变体 CREB133 和 KCREB 抑制 CacyBP/SIP 启动子活性。为了检查 CacyBP/SIP 表达/水平升高的生物学意义，我们应用了 RNA 微阵列分析，发现 CacyBP/SIP 的上调导致许多参与免疫过程等的基因的 mRNA 水平发生变化。版权所有 2017 IUBMB Life，70（1）：50-59，2018。
