IKKalpha, a critical regulator of epidermal differentiation and a suppressor of skin cancer.
IKKalpha, a critical regulator of epidermal differentiation and a suppressor of skin cancer.
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DOI：
10.1038/emboj.2008.196
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发表时间：
2008-10-22
期刊：
影响因子：
11.4
通讯作者：
Karin, Michael
中科院分区：
文献类型：
--
作者：
Descargues, Pascal;Sil, Alok K.;Karin, Michael
IKK激酶α (IKKα)是参与核因子κB （NF-κB）活化的IKK复合物的两个催化亚基之一，也作为控制表皮分化的分子开关。这种意想不到的功能需要IKKα核易位，但不依赖于其激酶活性，并且独立于NF-κB信号传导。Ikkα - / -小鼠表皮增生，未分化，完全没有颗粒层和角质层。缺乏ikk α的角质形成细胞不表达终末分化标志物，即使受到诱导分化的刺激也会继续增殖。IKKα的这种抗增殖功能对抑制鳞状细胞癌变也很重要。核IKKα控制角质形成细胞增殖和分化的确切机制在一段时间内仍然是一个谜。然而，最近的研究表明，IKKα是TGFβ-Smad2/3信号通路的主要辅助因子，而Smad4独立。该途径控制角化细胞终末分化过程中的细胞周期退出。虽然这些不是核IKKα的唯一功能，但这种多功能蛋白是角质形成细胞和表皮分化的关键调节因子，也是皮肤癌的关键抑制因子。
IκB kinase α (IKKα), one of the two catalytic subunits of the IKK complex involved in nuclear factor κB (NF-κB) activation, also functions as a molecular switch that controls epidermal differentiation. This unexpected function requires IKKα nuclear translocation but does not depend on its kinase activity, and is independent of NF-κB signalling. Ikkα–/– mice present with a hyperproliferative and undifferentiated epidermis characterized by complete absence of a granular layer and stratum corneum. Ikkα-deficient keratinocytes do not express terminal differentiation markers and continue to proliferate even when subjected to differentiation-inducing stimuli. This antiproliferative function of IKKα is also important for the suppression of squamous cell carcinogenesis. The exact mechanisms by which nuclear IKKα controls keratinocyte proliferation and differentiation remained mysterious for some time. Recent studies, however, have revealed that IKKα is a major cofactor in a TGFβ–Smad2/3 signalling pathway that is Smad4 independent. This pathway controls cell cycle withdrawal during keratinocyte terminal differentiation. Although these are not the only functions of nuclear IKKα, this multifunctional protein is a key regulator of keratinocyte and epidermal differentiation and a critical suppressor of skin cancer.
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影响因子：
4
作者：
FUCHS, E;BYRNE, C
通讯作者：
BYRNE, C
DOI：
10.1073/pnas.0605333103
发表时间：
2006-08-22
影响因子：
11.1
作者：
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通讯作者：
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作者：
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通讯作者：
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影响因子：
10.5
作者：
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通讯作者：
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影响因子：
2.6
作者：
Hardisson, D
通讯作者：
Hardisson, D