Sublethal UV irradiation induces squamous differentiation via a p53-independent, DNA damage-mitosis checkpoint.
Sublethal UV irradiation induces squamous differentiation via a p53-independent, DNA damage-mitosis checkpoint.
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DOI：
10.1038/s41419-018-1130-8
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发表时间：
2018-10-25
影响因子：
9
通讯作者：
Gandarillas A
中科院分区：
文献类型：
--
作者：
de Pedro I;Alonso-Lecue P;Sanz-Gómez N;Freije A;Gandarillas A
表皮是一种自我更新的上皮细胞，持续暴露于紫外线（UV）的遗传毒性作用，是皮肤癌的主要原因。因此，它需要强大的自我保护机制面对基因组损伤。已显示p53介导表皮晒伤细胞的凋亡。然而，表皮细胞每天接受亚致死诱变剂量的紫外线和大量的细胞凋亡将是有害的。我们最近解开了一个抗癌角质形成细胞DNA损伤分化的细胞周期应激反应。我们现在已经研究了这种反应，高或中等剂量的紫外线照射。然而，正如预期的那样，高水平的紫外线诱导p53依赖性细胞凋亡，中等水平引发鳞状细胞分化。紫外线诱导的分化是不介导的内源性p53。有丝分裂全局调节因子FOXM1的过表达减轻了由UV引起的增殖损失。相反，敲低有丝分裂检查点蛋白Wee1驱动UV诱导的分化为凋亡。因此，结果表明，有丝分裂检查点决定了对紫外线照射的反应。在头颈部上皮细胞中也发现了分化反应，从而揭示了慢性暴露于诱变剂后鳞状组织中的常见调节，并涉及稳态和疾病。
The epidermis is a self-renewal epithelium continuously exposed to the genotoxic effects of ultraviolet (UV) light, the main cause of skin cancer. Therefore, it needs robust self-protective mechanisms facing genomic damage. p53 has been shown to mediate apoptosis in sunburn cells of the epidermis. However, epidermal cells daily receive sublethal mutagenic doses of UV and massive apoptosis would be deleterious. We have recently unravelled an anti-oncogenic keratinocyte DNA damage-differentiation response to cell cycle stress. We now have studied this response to high or moderate single doses of UV irradiation. Whereas, as expected, high levels of UV induced p53-dependent apoptosis, moderate levels triggered squamous differentiation. UV-induced differentiation was not mediated by endogenous p53. Overexpression of the mitosis global regulator FOXM1 alleviated the proliferative loss caused by UV. Conversely, knocking-down the mitotic checkpoint protein Wee1 drove UV-induced differentiation into apoptosis. Therefore, the results indicate that mitosis checkpoints determine the response to UV irradiation. The differentiation response was also found in cells of head and neck epithelia thus uncovering a common regulation in squamous tissues upon chronic exposure to mutagens, with implications into homeostasis and disease.
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DOI：
10.1083/jcb.127.3.789
发表时间：
1994-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Andreassen PR;Margolis RL
通讯作者：
Margolis RL
影响因子：
--
作者：
HUDSON, DL;WEILAND, KL;WATT, FM
通讯作者：
WATT, FM
影响因子：
6.6
作者：
Aylon Y;Oren M
通讯作者：
Oren M
影响因子：
6.5
作者：
Berton, TP;Pavone, A;Fischer, SM
通讯作者：
Fischer, SM
影响因子：
50.5
作者：
Ferlay, J.;Autier, P.;Boyle, P.
通讯作者：
Boyle, P.