The canonical Notch signaling pathway: unfolding the activation mechanism.

The canonical Notch signaling pathway: unfolding the activation mechanism.
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DOI:
10.1016/j.cell.2009.03.045
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发表时间:
2009-04-17
期刊:
影响因子:
64.5
通讯作者:
Ilagan MX
Ilagan MX
中科院分区:
生物学1区
文献类型:
--
作者:
Kopan R;Ilagan MX

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Notch信号调节后生动物发育和组织更新的许多方面。因此,Notch信号传导的失调或缺失是多种人类病症的基础,从发育综合征到成人发病疾病和癌症。Notch受体活化是不可逆的,因为它涉及Notch细胞内结构域的蛋白水解介导的释放、易位到细胞核以及与DNA结合蛋白的缔合。尽管每个Notch分子仅发出一次信号,而不通过第二信使级联放大,但Notch信号在大多数组织中非常稳健。在这篇综述中,我们强调了最近的研究,揭示了新的分子细节参与调节配体介导的激活,受体蛋白水解和靶点选择。
Notch signaling regulates many aspects of metazoan development and tissue renewal. Accordingly, misregulation or loss of Notch signaling underlies multiple human disorders, from developmental syndromes to adult onset diseases and cancer. Notch receptor activation is irreversible as it involves proteolysis-mediated release of the Notch intracellular domain, translocation to the nucleus, and association with a DNA-bound protein. Even though each Notch molecule signals only once without amplification by secondary messenger cascades, Notch signaling is remarkably robust in most tissues. In this review, we highlight the recent studies that reveal new molecular details involved in regulating ligand-mediated activation, receptor proteolysis and target selection.
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