An insulin-inducible transcription factor, SHARP-1, represses transcription of the SIRT1 longevity gene.
An insulin-inducible transcription factor, SHARP-1, represses transcription of the SIRT1 longevity gene.
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胰岛素诱导转录因子 SHARP-1 可抑制 SIRT1 长寿基因的转录。
DOI：
10.1016/j.bbrep.2020.100743
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
K.
中科院分区：
文献类型：
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作者：
Asano;K.;Tsukada;A.;Takagi;K.;and Yamada;K.
SHARP-1基因编码胰岛素诱导的转录抑制因子。长寿基因sirtuin 1（SIRT 1）编码蛋白质脱乙酰酶。这些在调节肝脏葡萄糖代谢中起重要作用。在这项研究中，为了评估与这些基因表达的相关性，我们研究了SIRT 1是否影响SHARP-1基因的表达与SIRT 1抑制剂或激活剂在大鼠H4 IIE肝癌细胞的治疗。SIRT 1抑制剂可增加SHARP-1 mRNA的表达水平，而SIRT 1激活剂则可降低SHARP-1 mRNA的表达水平。SIRT 1基因启动子活性被SHARP-1特异性抑制。利用5′-缺失或突变的构建体进行的进一步的报告基因分析显示，SHARP-1的抑制作用需要SIRT 1基因启动子的E盒序列（5′-CACGTG-3′）。因此，我们认为SHARP-1和SIRT 1基因的表达呈负相关，SHARP-1抑制SIRT 1基因的转录。
The ratenhancer of split- and hairy-related protein (SHARP)-1genes encode insulin-inducible transcriptional repressors. A longevity gene,sirtuin 1 (SIRT1)encodes protein deacetylase. These play an important role in regulating hepatic glucose metabolism. In this study, to evaluate a correlation with these gene expressions, we examined whether SIRT1 effects on expression of theSHARP-1 gene by a treatment with a SIRT1 inhibitor or activator in rat H4IIE hepatoma cells. Whereas the SIRT1 inhibitor increased the level of SHARP-1 mRNA, the SIRT1 activator decreased it. Next, whether SHARP-1 effect on the transcriptional activity of the humanSIRT1gene using luciferase reporter assays was determined. Promoter activity of theSIRT1gene was specifically repressed by SHARP-1. Further reporter analysis using 5′- deleted or mutated constructs revealed that an E box sequence (5′-CACGTG-3′) of theSIRT1gene promoter was required for the inhibitory effect of SHARP-1. Thus, we conclude that expressions between theSHARP-1and theSIRT1genes show a negative correlation and that SHARP-1 represses transcription of theSIRT1gene.