Regulation of epidermal apoptosis and DNA repair by E2F1 in response to ultraviolet B radiation
Regulation of epidermal apoptosis and DNA repair by E2F1 in response to ultraviolet B radiation
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DOI：
10.1038/sj.onc.1208462
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发表时间：
2005-04-07
期刊：
影响因子：
8
通讯作者：
Johnson, DG
中科院分区：
文献类型：
--
作者：
Berton, TR;Mitchell, DL;Johnson, DG
E2F1转录因子调节参与细胞增殖、凋亡和DNA修复的基因的表达。 DNA 损伤后，E2F1 被磷酸化并稳定，但 E2F1 在 DNA 损伤反应中的生理作用尚不清楚。我们发现，与野生型小鼠相比，缺乏 E2F1 的小鼠在暴露于紫外线 B (UVB) 辐射后表皮细胞凋亡水平增加。此外，基底层角质形成细胞中 E2F1 的转基因过表达可抑制 UVB 诱导的细胞凋亡。鉴于大多数研究已证明 E2F1 具有促凋亡功能，E2F1 对 UVB 诱导的细胞凋亡的抑制是出乎意料的。 E2F1 介导的细胞凋亡抑制不涉及丝裂原激活蛋白激酶激活的改变或响应 UVB 的 Bcl-2 下调，并且不依赖于 p53。相反，E2F1 对 UVB 诱导的细胞凋亡的抑制与刺激 DNA 修复相关。缺乏E2F1的小鼠去除DNA光产物的能力受到损害，而与野生型小鼠相比，E2F1转基因小鼠以更快的速度修复UVB诱导的DNA损伤。这些发现表明 E2F1 通过促进 DNA 修复和抑制细胞凋亡来参与 UVB 反应。
The E2F1 transcription factor regulates the expression of genes involved in cell proliferation, apoptosis and DNA repair. Following DNA damage, E2F1 is phosphorylated and stabilized, but the physiological role of E2F1 in the response to DNA damage is unclear. We find that mice lacking E2F1 have increased levels of epidermal apoptosis compared to wild-type mice following exposure to ultraviolet B (UVB) radiation. Moreover, transgenic overexpression of E2F1 in basal layer keratinocytes suppresses apoptosis induced by UVB. Inhibition of UVB-induced apoptosis by E2F1 is unexpected given that most studies have demonstrated a proapoptotic function for E2F1. E2F1-mediated suppression of apoptosis does not involve alterations in mitogen-activated protein kinase activation or Bcl-2 downregulation in response to UVB and is independent of p53. Instead, inhibition of UVB-induced apoptosis by E2F1 correlates with a stimulation of DNA repair. Mice lacking E2F1 are impaired for the removal of DNA photoproducts, while E2F1 transgenic mice repair UVB-induced DNA damage at an accelerated rate compared to wild-type mice. These findings suggest that E2F1 participates in the response to UVB by promoting DNA repair and suppressing apoptosis.