Hairless: the ignored antagonist of the Notch signalling pathway
Hairless: the ignored antagonist of the Notch signalling pathway
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DOI：
10.1111/j.2007.0018-0661.01971.x
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发表时间：
2006-01-01
期刊：
影响因子：
2.7
通讯作者：
Maier, Dieter
中科院分区：
文献类型：
--
作者：
Maier, Dieter
Notch信号通路调节高等真核生物中的细胞间通讯。细胞分化和组织发育依赖于正确的细胞间通讯，这也是Notch信号通路受到高度关注的原因。Notch与masterd和CSL（CBF-1，Suppressor of Hairless，lag-2）DNA结合蛋白一起形成复合物，介导相应靶基因的转录激活。这种激活受到严格的控制，放松管制会导致极端的发育缺陷。在果蝇中，控制系统的严格性由一般的Notch拮抗剂Hairless给出。Hairless在Notch靶基因上组装成一个阻遏物复合物，该复合物包括Hairless的阻遏物和两个辅阻遏物Groucho和C-末端结合蛋白。在哺乳动物中，CBF-1自行招募辅阻遏物。此外，无毛还招募其他蛋白质。一个例子是Pros26.4 AAA-ATP酶，其特异性地使无毛不稳定，导致Notch信号传导的新的正调节。通过抑制Notch，Hairless不仅调节细胞分化，而且具有抗凋亡功能。此外，许多遗传相互作用意味着Hairless和EGF受体途径之间的交叉对话，这可能独立于Notch发挥作用。令人惊讶的是，尽管该途径的其他组分高度保守，但到目前为止还没有在哺乳动物中鉴定出无毛同源物。一旦不同物种中阻遏物复合物的所有成分都被鉴定出来，这种差异可能在未来得到解决。总之，无毛是调节果蝇Notch信号通路的核心成分，因此对果蝇的细胞分化和组织发育至关重要。
The Notch signalling pathway regulates cell-cell communication in higher eukaryotes. Cellular differentiation and tissue development relies on correct intercellular communication, accounting for the high interest in the Notch signalling pathway. Together with mastermind and CSL (CBF-1, Suppressor of Hairless, lag-2) DNA-binding proteins, Notch forms a complex that mediates transcriptional activation of the respective target genes. This activation is strictly controlled, and deregulation causes extreme developmental defects. In Drosophila, the stringency of the control system is given by the general Notch-antagonist Hairless. Hairless assembles in a repressor complex on Notch target genes, which involves Suppressor of Hairless and two corepressors, Groucho and C-terminal binding protein. In mammals, CBF-1 recruits corepressors on its own. In addition Hairless recruits also other proteins. One example is the Pros26.4 AAA-ATPase which specifically destabilises Hairless resulting in a novel positive regulation of Notch signalling. By inhibition of Notch, Hairless not only regulates cellular differentiation but also has anti-apoptotic functions. Moreover, many genetic interactions imply a cross-talk between Hairless and the EGF-receptor pathway, which might act independently of Notch. Surprisingly, no Hairless homologue has been identified in mammals so far, despite the high degree of conservation of other components of the pathway. This discrepancy might be resolved in the future, once all components of the repressor-complex in the different species have been identified. In conclusion, Hairless is a central component of the regulation of the Notch signalling pathway in Drosophila, and is hence essential for cell differentiation and tissue development in the fly.