角质形成细胞分化过程中Notch与p63之间的交叉调控。
Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation.
作者信息
Nguyen Bach-Cuc, Lefort Karine, Mandinova Anna, Antonini Dario, Devgan Vikram, Della Gatta Giusy, Koster Maranke I, Zhang Zhuo, Wang Jian, Tommasi di Vignano Alice, Kitajewski Jan, Chiorino Giovanna, Roop Dennis R, Missero Caterina, Dotto G Paolo
机构信息
Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA, and Department of Biochemistry, University of Lausanne, Switzerland.
出版信息
Genes Dev. 2006 Apr 15;20(8):1028-42. doi: 10.1101/gad.1406006.
Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment of the keratinocyte cell fate and/or maintenance of epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation in both mouse and human keratinocytes through a mechanism independent of cell cycle withdrawal and requiring down-modulation of selected interferon-responsive genes, including IRF7 and/or IRF3. In turn, elevated p63 expression counteracts the ability of Notch1 to restrict growth and promote differentiation. p63 functions as a selective modulator of Notch1-dependent transcription and function, with the Hes-1 gene as one of its direct negative targets. Thus, a complex cross-talk between Notch and p63 is involved in the balance between keratinocyte self-renewal and differentiation.
Notch信号通路促进角质形成细胞向分化方向发展，并抑制肿瘤发生。p63是p53家族成员之一，与角质形成细胞命运的建立和/或上皮自我更新的维持有关。在此我们表明，在小鼠和人类角质形成细胞中，Notch1激活通过一种独立于细胞周期退出的机制抑制p63表达，该机制需要下调包括IRF7和/或IRF3在内的特定干扰素反应基因。反过来，p63表达升高会抵消Notch1限制生长和促进分化的能力。p63作为Notch1依赖性转录和功能的选择性调节因子，Hes-1基因是其直接负靶标之一。因此，Notch和p63之间复杂的相互作用参与了角质形成细胞自我更新和分化之间的平衡。
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