Fas ligand: A sensor for DNA damage critical in skin cancer etiology
Fas ligand: A sensor for DNA damage critical in skin cancer etiology
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DOI：
10.1126/science.285.5429.898
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发表时间：
1999-08-06
期刊：
影响因子：
56.9
通讯作者：
Owen-Schaub, LB
中科院分区：
文献类型：
--
作者：
Hill, LL;Ouhtit, A;Owen-Schaub, LB
DNA受损的细胞可以修复DNA或通过称为“细胞校正”的稳态控制机制被清除。“紫外线辐射（UVR）后，通过晒伤细胞（凋亡角质形成细胞）的形成消除DNA损伤细胞被认为是去除癌前皮肤细胞的关键。晒伤细胞的形成被认为是依赖于Fas配体（FasL），一种由DNA损伤诱导的促凋亡蛋白。长期暴露于紫外线照射导致20只FasL缺陷小鼠中的14只（70%）和20只野生型小鼠中的1只（5%）在表皮中积累p53突变。因此，Fast-mediated凋亡对皮肤稳态很重要，表明Fas-FasL相互作用的失调可能是皮肤癌发展的核心。
DNA-damaged cells can either repair the DNA or be eliminated through a homeostatic control mechanism termed "cellular proofreading." Elimination of DNA-damaged cells after ultraviolet radiation (UVR) through sunburn cell (apoptotic keratinocyte) formation is thought to be pivotal for the removal of precancerous skin cells. Sunburn cell formation was found to be dependent on Fas ligand (FasL), a pro-apoptotic protein induced by DNA damage. Chronic exposure to UVR caused 14 of 20 (70 percent) FasL-deficient mice and 1 of 20 (5 percent) wild-type mice to accumulate p53 mutations in the epidermis, Thus, Fast-mediated apoptosis is important for skin homeostasis, suggesting that the dysregulation of Fas-FasL interactions may be central to the development of skin cancer.