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鉴定出两种缺少N端结构域的小鼠NUR77新亚型。

Identification of two novel isoforms of mouse NUR77 lacking N-terminal domains.

作者信息

Rehman Sayeed Ur, Sarwar Tarique, Husain Mohammed Amir, Ishqi Hassan Mubarak, Tabish Mohammad

机构信息

Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, Uttar Pradesh, India.

Department of Biosciences, Jamia Millia Islamia, New Delhi, Delhi, India.

出版信息

IUBMB Life. 2017 Feb;69(2):106-114. doi: 10.1002/iub.1605. Epub 2017 Jan 23.

Abstract

Nur77 is a member of nuclear receptor superfamily that acts as a transcription factor and regulates expression of multiple genes. Subcellular localization of Nur77 protein plays an important role in the survival and cell death. In this study, we have predicted and confirmed alternatively spliced two new transcripts of Nur77 gene in mouse. The newly identified transcripts have their alternatively spliced first exon located upstream of published 5'-UTR of the gene. Transcription factor binding sites in the possible promoter regions of these transcripts were also analyzed. Expression of novel transcript variants was found to be significantly lower than the already published transcript. New transcript variants encode for NUR77 protein isoforms which are significantly smaller in size due to lack of transactivation domain and a part of DNA binding domain. Western blot analysis using NUR77 specific antibody confirmed the existence of these smaller variants in mouse. Localization of these new isoforms was predicted to be majorly outside the nucleus. In silico analysis of the conceptually translated proteins was performed using different bioinformatics tools. The results obtained in this study offer further insight into novel area of research on extensively studied Nur77. © 2017 IUBMB Life, 69(2):106-114, 2017.

摘要

Nur77是核受体超家族的成员,作为一种转录因子,调控多个基因的表达。Nur77蛋白的亚细胞定位在细胞存活和死亡中起重要作用。在本研究中,我们预测并证实了小鼠中Nur77基因的两个新的可变剪接转录本。新鉴定的转录本具有可变剪接的第一个外显子,位于该基因已发表的5'-UTR上游。还分析了这些转录本可能的启动子区域中的转录因子结合位点。发现新转录本变体的表达明显低于已发表的转录本。新转录本变体编码的NUR77蛋白异构体由于缺乏反式激活结构域和部分DNA结合结构域,其大小明显更小。使用NUR77特异性抗体进行的蛋白质免疫印迹分析证实了小鼠中存在这些较小的变体。预计这些新异构体主要定位于细胞核外。使用不同的生物信息学工具对概念性翻译的蛋白质进行了计算机分析。本研究获得的结果为深入研究广泛研究的Nur77提供了新的研究领域。©2017国际生物化学与分子生物学联盟生命科学,69(2):106 - 114,2017。

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