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鉴定和描述血吸虫寄生虫中的 Mef2 转录激活因子。

Identification and characterization of a Mef2 transcriptional activator in schistosome parasites.

机构信息

Department of Biology, Case Western Reserve University, Cleveland, Ohio, USA.

出版信息

PLoS Negl Trop Dis. 2012 Jan;6(1):e1443. doi: 10.1371/journal.pntd.0001443. Epub 2012 Jan 3.

Abstract

Myocyte enhancer factor 2 protein (Mef2) is an evolutionarily conserved activator of transcription that is critical to induce and control complex processes in myogenesis and neurogenesis in vertebrates and insects, and osteogenesis in vertebrates. In Drosophila, Mef2 null mutants are unable to produce differentiated muscle cells, and in vertebrates, Mef2 mutants are embryonic lethal. Schistosome worms are responsible for over 200 million cases of schistosomiasis globally, but little is known about early development of schistosome parasites after infecting a vertebrate host. Understanding basic schistosome development could be crucial to delineating potential drug targets. Here, we identify and characterize Mef2 from the schistosome worm Schistosoma mansoni (SmMef2). We initially identified SmMef2 as a homolog to the yeast Mef2 homolog, Resistance to Lethality of MKK1P386 overexpression (Rlm1), and we show that SmMef2 is homologous to conserved Mef2 family proteins. Using a genetics approach, we demonstrate that SmMef2 is a transactivator that can induce transcription of four separate heterologous reporter genes by yeast one-hybrid analysis. We also show that Mef2 is expressed during several stages of schistosome development by quantitative PCR and that it can bind to conserved Mef2 DNA consensus binding sequences.

摘要

肌细胞增强因子 2 蛋白(Mef2)是一种进化上保守的转录激活因子,对于脊椎动物和昆虫的肌发生和神经发生以及脊椎动物的成骨作用中的复杂过程的诱导和控制至关重要。在果蝇中,Mef2 缺失突变体无法产生分化的肌肉细胞,而在脊椎动物中,Mef2 突变体是胚胎致死的。血吸虫是导致全球超过 2 亿例血吸虫病的罪魁祸首,但对于血吸虫寄生虫在感染脊椎动物宿主后的早期发育知之甚少。了解基本的血吸虫发育情况对于确定潜在的药物靶点可能至关重要。在这里,我们从血吸虫 Schistosoma mansoni(SmMef2)中鉴定和表征了 Mef2。我们最初将 SmMef2 鉴定为酵母 Mef2 同源物 Resistance to Lethality of MKK1P386 overexpression(Rlm1)的同源物,我们表明 SmMef2 与保守的 Mef2 家族蛋白同源。通过遗传学方法,我们证明 SmMef2 是一种反式激活因子,可通过酵母单杂交分析诱导四个独立的异源报告基因的转录。我们还表明,通过定量 PCR 显示 Mef2 在血吸虫发育的几个阶段表达,并且它可以与保守的 Mef2 DNA 共识结合序列结合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1527/3250504/19eaedd951c8/pntd.0001443.g001.jpg

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