Molecular function of stress protein A170 in skin carcinogenesis by UV radiation

本研究探讨A170在UVB诱导细胞凋亡中的作用。A170是已知的压力诱导基因，A170缺陷的小鼠表现出成熟的肥胖症。我们先前发现A170 KO小鼠来源的小鼠胚胎成纤维细胞(MEF)对UVB诱导的细胞死亡具有抵抗力。首先，我们分析了A170击倒的野生型MEF是否表现出与KO MEF相同的抗UVB辐射的特性。结果表明，基因敲除细胞也对UVB具有抗性。接下来，对参与细胞凋亡信号的蛋白质进行了分析。有趣的是，经UVB照射后，KO细胞中促凋亡蛋白如Bax、caspase的水平降低。此外，KO细胞中抗凋亡蛋白基因的表达水平明显高于WT细胞。我们发现转录因子STAT3在KO细胞中被显着激活，该转录因子正向调节抗凋亡基因的诱导。此外，体内分析表明，A170 KO小鼠的皮肤组织对UVB辐射的损伤相对较小。这些结果表明，A170是通过改变促凋亡和抗凋亡蛋白水平来调节凋亡信号的新的重要因子。

In this study, the role of A170 in UVB induced apoptosis was investigated. A170 is known to stress inducible gene, and A170 deficient mice show mature onset obesity. We previously found mouse embryonic fibroblast (MEF) derived from A170 KO mice were resistant to UVB induced cell death. At first, we analyzed whether A170 knocked down wild type MEF show same characters as KO MEF against UVB radiation. The results shows knockdown cells are also resistant to UVB. Next, the proteins involved in the apoptotic signal were analyzed. Interestingly, pro-apoptotic protein levels such as Bax, caspase after UVB exposure were reduced in KO cells. In addition, anti-apoptotic protein mRNA levels were markedly increased in KO cells compared with WT. We found transcription factor Stat3 which is known to positively regulates anti-apoptotic gene induction was remarkably activated in KO cells. Moreover, in vivo analysis revealed that A170 KO mice skin tissue show relatively low damage by UVB radiation. These results suggest that A170 is novel important factor for regulating apoptotic signal by altering pro- and anti-apoptotic protein levels.