Souid Sami, Lepesant Jean-Antoine, Yanicostas Constantin
Institut Jacques Monod, UMR 7592, CNRS, Université Denis-Diderot Paris 7 and Université Paris 6 Pierre et Marie Curie, 2, Place Jussieu, 75251, Paris Cedex 05, France.
Dev Genes Evol. 2007 Feb;217(2):159-67. doi: 10.1007/s00427-006-0124-1. Epub 2007 Jan 6.
We report in this paper the characterization of Dxbp-1, the Drosophila homologue of the xpb-1 gene that encodes a "bZIP"-containing transcription factor that plays a key role in the unfolded protein response (UPR), an evolutionarily conserved signalling pathway activated by an overload of misfolded proteins in the endoplasmic reticulum (ER). Dxbp-1 is ubiquitously transcribed, and high levels are found in embryonic salivary glands and in the ovarian follicle cells committed to the synthesis of the respiratory appendages. Loss of function of Dxbp-1 induced a recessive larval lethality, thus, revealing an essential requirement for this gene. The Dxbp-1 transcript was submitted to an "unconventional" splicing that generated a processed Dxbp-1s transcript encoding a DXbp-1 protein isoform, as is the case for yeast, Caenorhabditis elegans and vertebrate hac1/xbp-1 transcripts after UPR activation. However, in the absence of exogenously induced ER stress, the Dxbp-1s transcript was also detectable not only throughout embryonic and larval development but also in adults with a high level of accumulation in the male sexual apparatus and, to a lesser extent, in the salivary glands of the third-instar larvae. Using a Dxbp-1:GFP transgene as an in vivo reporter for Dxbp-1 mRNA unconventional splicing, we confirmed that Dxbp-1 processing took place in the salivary glands of the third-instar larvae. The Dxbp-1 gene appears, thus, to play an essential role during the development of Drosophila, hypothetically by stimulating the folding capacities of the ER in cells committed to intense secretory activities.
我们在本文中报告了Dxbp-1的特征,它是xpb-1基因的果蝇同源物,xpb-1基因编码一种含“bZIP”的转录因子,该转录因子在未折叠蛋白反应(UPR)中起关键作用,UPR是一种由内质网(ER)中错误折叠蛋白过载激活的进化保守信号通路。Dxbp-1在各处转录,在胚胎唾液腺和致力于呼吸附属器合成的卵巢卵泡细胞中含量很高。Dxbp-1功能丧失导致隐性幼虫致死,因此揭示了该基因的基本需求。Dxbp-1转录本经历了“非常规”剪接,产生了加工后的Dxbp-1s转录本,其编码DXbp-1蛋白异构体,酵母、秀丽隐杆线虫和脊椎动物hac1/xbp-1转录本在UPR激活后也是如此。然而,在没有外源性诱导的内质网应激的情况下,不仅在整个胚胎和幼虫发育过程中,而且在成体中,Dxbp-1s转录本也可检测到,在雄性性器官中积累水平很高,在三龄幼虫的唾液腺中积累程度较低。使用Dxbp-1:GFP转基因作为Dxbp-1 mRNA非常规剪接的体内报告基因,我们证实了Dxbp-1加工发生在三龄幼虫的唾液腺中。因此,Dxbp-1基因似乎在果蝇发育过程中起重要作用,推测是通过刺激致力于强烈分泌活动的细胞内质网的折叠能力来实现的。