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

本研究探讨了A170在UVB诱导的细胞凋亡中的作用。已知A170是应激诱导基因，A170缺陷小鼠表现出成熟型肥胖。我们以前发现A170基因敲除小鼠的胚胎成纤维细胞（MEF）对UVB诱导的细胞死亡具有抵抗力。我们首先分析了A170敲除的野生型MEF是否表现出与KO MEF相同的抗UVB特性。结果显示敲除细胞也对UVB具有抗性。接下来，分析参与凋亡信号的蛋白质。有趣的是，在KO细胞中，UVB暴露后促凋亡蛋白如Bax、caspase水平降低。此外，与WT相比，KO细胞中抗凋亡蛋白mRNA水平显著增加。我们发现转录因子Stat3，这是已知的积极调节抗凋亡基因的诱导显着激活KO细胞。此外，体内分析显示，A170 KO小鼠皮肤组织显示出UVB辐射的相对低的损伤。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.