Regulation of notch signalling by non-visual β-arrestin
Regulation of notch signalling by non-visual β-arrestin
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DOI：
10.1038/ncb1327
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发表时间：
2005-12-01
影响因子：
21.3
通讯作者：
Artavanis-Tsakonas, S
中科院分区：
文献类型：
--
作者：
Mukherjee, A;Veraksa, A;Artavanis-Tsakonas, S
在后生动物细胞命运决定中起重要作用的Notch受体的信号活性在多个水平上受到控制。我们发现了一种Notch信号控制机制，该机制依赖于非视觉P-arrestin Kurtz(KRZ)影响Notch受体降解的能力，从而影响Notch受体的功能。我们确定KRZ是已知的Notch途径调节剂Deltex(Dx)的结合伙伴，并证明了Notch-Dx-KRZ蛋白复合体的存在。该复合体通过泛素化依赖的途径介导Notch受体的降解。我们的结果建立了一种新的Notch信号调节模式，并为非视觉β-拦阻蛋白定义了一种新的功能。
Signalling activity of the Notch receptor, which plays a fundamental role in metazoan cell fate determination, is controlled at multiple levels. We uncovered a Notch signal-controlling mechanism that depends on the ability of the non-visual P-arrestin, Kurtz (Krz), to influence the degradation and, consequently, the function of the Notch receptor. We identified Krz as a binding partner of a known Notch-pathway modulator, Deltex (Dx), and demonstrated the existence of a trimeric Notch-Dx-Krz protein complex. This complex mediates the degradation of the Notch receptor through a ubiquitination-dependent pathway. Our results establish a novel mode of regulation of Notch signalling and define a new function for non-visual beta-arrestins.