IKK1 control of epidermal differentiation is modulated by notch signaling.
IKK1 control of epidermal differentiation is modulated by notch signaling.
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IKK1 对表皮分化的控制由 Notch 信号传导调节。
DOI：
10.1016/j.ajpath.2010.12.021
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Li,Qiutang
中科院分区：
文献类型：
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作者：
Xin,Ying;Lu,Qingxian;Li,Qiutang
IκB激酶1（IKK 1）调节皮肤表皮分化和肿瘤抑制的分子机制尚不清楚。作为调节表皮稳态和分化的两个主要调节信号通路，p63和Notch通路在Ikk 1突变表皮和角质形成细胞中被检测。角质形成细胞中Ikk 1失活导致p63表达增加和Notch信号转导抑制。Ikk 1 −/−角质形成细胞的分化受损部分通过Notch 1受体的活性形式Notch胞内结构域（NICD）的过表达而得到挽救。相反，通过RNA干扰敲低p63表达不能挽救缺陷。这些结果表明，在哺乳动物皮肤中，IKK 1通过Notch信号通路作为分化调节剂和肿瘤抑制剂发挥作用。
The molecular mechanism by which IκB kinase 1 (IKK1) regulates epidermal differentiation and tumor suppression in the skin is not well understood. As two major regulatory signaling pathways that regulate epidermal homeostasis and differentiation, the p63 and Notch pathways were examined in Ikk1 mutant epidermis and keratinocytes. Ikk1 inactivation in keratinocytes resulted in increased p63 expression and repression of Notch signaling. The impaired differentiation of Ikk1−/−keratinocytes was partially rescued by overexpression of the active form of the Notch1 receptor, the Notch intracellular domain (NICD). In contrast, knockdown of p63 expression by RNA interference was unable to rescue the defect. These results suggest that, in the mammalian skin, IKK1 functions as a differentiation regulator and tumor suppressor through the Notch signaling pathway.