Sumoylation of Pdx1 is associated with its nuclear localization and insulin gene activation
Sumoylation of Pdx1 is associated with its nuclear localization and insulin gene activation
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DOI：
10.1152/ajpendo.00390.2002
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发表时间：
2003-04-01
影响因子：
5.1
通讯作者：
Kashiwagi, A
中科院分区：
文献类型：
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作者：
Kishi, A;Nakamura, T;Kashiwagi, A
胰十二指肠同源盒-1 （Pdx1）是一种转录因子，其磷酸化被认为是胰岛素基因表达激活的必要条件。这种磷酸化与分子质量从31 kDa到46 kDa的变化有关。然而，我们发现Pdx1在β - tc -6和COS-7细胞中被SUMO-1（小泛素相关修饰物1）修饰，这些细胞被Pdx1 cDNA转染。这一修饰使Pdx1的分子质量从31增加到46 kDa。此外，summoylated Pdx1定位于细胞核。使用RNA干扰（SUMO-iRNAs）减少SUMO-1蛋白导致细胞核中Pdx1蛋白显著减少。暴露于SUMO-iRNAs的细胞在乳糖蛋白酶抑制剂（一种蛋白酶体抑制剂）的存在下检测到34 kda形式的Pdx1。此外，核代谢Pdx1含量的降低与胰岛素基因转录活性的显著降低有关。这些发现表明SUMO-1修饰与Pdx1的定位和稳定性以及其对胰岛素基因激活的影响有关。
Pancreatic duodenal homeobox-1 (Pdx1) is a transcription factor, and its phosphorylation is thought to be essential for activation of insulin gene expression. This phosphorylation is related to a concomitant shift in molecular mass from 31 to 46 kDa. However, we found that Pdx1 was modified by SUMO-1 (small ubiquitin-related modifier 1) in beta-TC-6 and COS-7 cells, which were transfected with Pdx1 cDNA. This modification contributed to the increase in molecular mass of Pdx1 from 31 to 46 kDa. Additionally, sumoylated Pdx1 localized in the nucleus. The reduction of SUMO-1 protein by use of RNA interference (SUMO-iRNAs) resulted in a significant decrease in Pdx1 protein in the nucleus. A 34-kDa form of Pdx1 was detected by the cells exposed to SUMO-iRNAs in the presence of lactacystin, a proteasome inhibitor. Furthermore, the reduced nuclear sumoylated Pdx1 content was associated with significant lower transcriptional activity of the insulin gene. These findings indicate that SUMO-1 modification is associated with both the localization and stability of Pdx1 as well as its effect on insulin gene activation.