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首页> 外文期刊>Molecular Biology >The Influence of the Minor Short Isoform of Securin (PTTG1) on Transcription is Significantly Different from the Impact of the Full Isoform
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The Influence of the Minor Short Isoform of Securin (PTTG1) on Transcription is Significantly Different from the Impact of the Full Isoform

机译：Securin（PTTG1）对转录的次要短同种型的影响与全同种型的影响显着不同

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PTTG1 (vertebrate securin) is a separation inhibitor and regulates DNA repair and transcription. The protein is predominantly expressed in the second half of the S phase and at the G2 stage. With the onset of anaphase, securin is ubiquitinated by the APC/C complex and degraded rapidly. Increased expression of PTTG1 is associated with enhanced tumor cell growth and metastasis. Recently, we found a short securin isoform lacking the main APC/C recognition site (D-box) and the DNA-binding domain encoded by exons 3 and 4. The mRNA level of the short isoform in unsynchronized cells is 0.4-2% of the full-length one. We reported earlier on the ability of the short PTTG1 isoform to activate some of the genes controlled by the full-length protein. In this work, groups of genes, whose expression is altered by the action of the short and complete securin isoforms, were determined using RNA sequencing. Groups of genes whose mRNA levels are regulated by both protein isoforms and only one of the isoforms were identified. For a more detailed study of the effect of securin isoforms on the transcriptional program of cells, the NFYB gene, encoding the NF-Y transcription regulator subunit, was chosen. Our data showed that with overexpression of the short isoform, the level of NFYB mRNA decreased 2.4 +/- 0.7 times, while the complete isoform did not significantly affect the expression of NFYB. 2.2-fold suppression of the short isoform of securin led to an increase in the expression of NFYB mRNA by 2.7 +/- 0.3 times. Moreover, the mRNA expression of full-length securin increased by 2.7 +/- 0.4 times. Since NFYB is associated with the PTTG1 promoter region, we suggest that the short isoform may be involved in regulation of the expression of the main isoform of securin by changing the level of this transcription factor. Since NFYB and PTTG1 are involved in the development of tumors and the formation of drug resistance, we assume that the short isoform of securin may play an important role in these processes. Thus, we showed the functional significance of the minor short isoform of securin.
机译：PTTG1（脊椎动物Securin）是分离抑制剂并调节DNA修复和转录。蛋白质主要在S期的下半部分和G2阶段表达。随着后期的发作，Securin被APC / C复合物染色并迅速降解。 PTTG1的增加与增强的肿瘤细胞生长和转移相关。最近，我们发现缺乏主要APC / C识别位点（D-Box）和由外显子3和4编码的DNA结合域的短Securin同种型。非同步细胞中短同种型的mRNA水平为0.4-2％全长一个。我们之前报道了短PTTG1同种型活化全长蛋白控制的一些基因的能力。在这项工作中，使用RNA测序测定通过短和完全Securin同种型的作用改变的基因组，其表达式改变。鉴定了蛋白质同种型的mRNA水平和只有一种同种型的mRNA水平的基因组。为了更详细地研究Securin同种型对细胞转录程序的影响，选择了编码NF-Y转录调节亚基的NFYB基因。我们的数据显示，随着短同种型的过表达，NFYB mRNA的水平降低了2.4 +/- 0.7倍，而完整的同种型没有显着影响NFYB的表达。 2.2倍抑制Securin的短同种型导致NFYB mRNA表达增加2.7 +/- 0.3倍。此外，全长Securin的mRNA表达增加2.7 +/- 0.4倍。由于NFYB与PTTG1启动子区域相关，我们建议短同种型可以通过改变该转录因子的水平来涉及Securin的主要同种型的表达。由于NFYB和PTTG1涉及肿瘤的发育和耐药性的形成，因此假设Securin的短同种型可能在这些过程中起重要作用。因此，我们展示了Securin的次短同种型的功能意义。

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