Recognition and ubiquitination of notch by Itch, a hect-type E3 ubiquitin ligase
Recognition and ubiquitination of notch by Itch, a hect-type E3 ubiquitin ligase
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DOI：
10.1074/jbc.m007300200
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发表时间：
2000-11-17
影响因子：
4.8
通讯作者：
Liu, YC
中科院分区：
文献类型：
--
作者：
Qiu, L;Joazeiro, C;Liu, YC
遗传学研究证实了Itch，这是一种与EG相关蛋白羧基末端(Hect)结构域包含E3泛素蛋白连接酶的同源基因，在非刺鼠致死小鼠或瘙痒小鼠中被破坏。瘙痒不足会导致免疫反应异常和皮肤持续瘙痒。在这里，Itch被证明与Notch有关，Notch是一种在许多哺乳动物细胞类型中参与决定细胞命运的蛋白质，包括免疫系统中的细胞。ITCH通过其WW结构域与Notch胞内域的N端部分结合，并通过其Hect泛素连接酶结构域促进Notch的泛素化。因此，Itch可能通过改变Notch介导的信号转导途径参与免疫反应的调节。
Genetic studies identified Itch, which is a homologous to the EG-associated protein carboxyl terminus (Hect) domain-containing E3 ubiquitin-protein ligase that is disrupted in non-agouti lethal mice or Itchy mice. Itch-deficiency results in abnormal immune responses and constant itching in the skin. Here, Itch was shown to associate with Notch, a protein involved in cell fate decision in many mammalian cell types, including cells in the immune System. Itch binds to the N-terminal portion of the Notch intracellular domain via its WW domains and promotes ubiquitination of Notch through its Hect ubiquitin ligase domain. Thus, Itch may participate in the-regulation of immune responses by modifying Notch-mediated signaling.