Xeroderma pigmentosum complementation group A (XPA), is defective in xeroderma pigmentosum patients, causing pre-disposition to skin cancer and neurological abnormalities, which is not well understood. Here, we analyzed the XPA-deficient cells transcriptional profile under oxidative stress. The imbalance in of ubiquitin-proteasome system (UPS) gene expression was observed in XPA-deficient cells and the involvement of nuclear factor erythroid 2-related factor-2 (NFE2L2) was indicated. Co-immunoprecipitation assays showed the interaction between XPA, apurinic-apyrimidinic endonuclease 1 (APE1) and NFE2L2 proteins. Decreased NFE2L2 protein expression and proteasome activity was also observed in XPA-deficient cells. The data suggest the involvement of the growth arrest and DNA-damage-inducible beta (GADD45β) in NFE2L2 functions. Similar results were obtained in xpa-1 (RNAi) Caenorhabditis elegans suggesting the conservation of XPA and NFE2L2 interactions. In conclusion, stress response activation occurs in XPA-deficient cells under oxidative stress; however, these cells fail to activate the UPS cytoprotective response, which may contribute to XPA patient’s phenotypes.

皮肤干燥色素A补充剂（XPA），在皮肤干燥色素中有缺陷导致皮肤癌和神经系统异常的易感性，这尚未得到很好的理解。在这里，我们分析了氧化应激下XPA缺陷的细胞转录谱。在缺乏XPA的细胞中观察到了泛素-蛋白酶体系统（UPS）基因表达的失衡，并指出了核因子红系2相关因子2（NFE2L2）的参与。免疫共沉淀分析表明XPA，嘌呤-嘧啶核苷内切酶1（APE1）和NFE2L2蛋白之间存在相互作用。在XPA缺陷细胞中也观察到NFE2L2蛋白表达和蛋白酶体活性的降低。数据表明NFE2L2功能涉及生长停滞和DNA损伤诱导型beta（GADD45β）。在xpa-1（RNAi）中获得了相似的结果秀丽隐杆线虫提示XPA和NFE2L2相互作用的保守性。总之，应激反应激活发生在氧化应激下的XPA缺陷细胞中。但是，这些细胞不能激活UPS的细胞保护反应，这可能有助于XPA患者的表型。