Botch是一种γ-谷氨酰环转移酶，可去除甘氨酸并拮抗Notch。
Botch is a γ-glutamyl cyclotransferase that deglycinates and antagonizes Notch.
作者信息
Chi Zhikai, Byrne Sean T, Dolinko Andrew, Harraz Maged M, Kim Min-Sik, Umanah George, Zhong Jun, Chen Rong, Zhang Jianmin, Xu Jinchong, Chen Li, Pandey Akhilesh, Dawson Ted M, Dawson Valina L
机构信息
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
出版信息
Cell Rep. 2014 May 8;7(3):681-8. doi: 10.1016/j.celrep.2014.03.048. Epub 2014 Apr 24.
Botch promotes embryonic neurogenesis by inhibiting the initial S1 furin-like cleavage step of Notch maturation. The biochemical process by which Botch inhibits Notch maturation is not known. Here, we show that Botch has γ-glutamyl cyclotransferase (GGCT) activity that deglycinates Notch, which prevents the S1 furin-like cleavage. Moreover, Notch is monoglycinated on the γ-glutamyl carbon of glutamate 1,669. The deglycinase activity of Botch is required for inhibition of Notch signaling both in vitro and in vivo. When the γ-glutamyl-glycine at position 1,669 of Notch is degylcinated, it is replaced by 5-oxy-proline. These results reveal that Botch regulates Notch signaling through deglycination and identify a posttranslational modification of Notch that plays an important role in neurogenesis.
Botch通过抑制Notch成熟的初始S1弗林蛋白酶样切割步骤来促进胚胎神经发生。Botch抑制Notch成熟的生化过程尚不清楚。在此，我们表明Botch具有γ-谷氨酰环转移酶（GGCT）活性，可去除Notch上的甘氨酸，从而阻止S1弗林蛋白酶样切割。此外，Notch在谷氨酸1669的γ-谷氨酰碳上被单糖基化。Botch的去糖基化酶活性在体外和体内抑制Notch信号传导中都是必需的。当Notch第1669位的γ-谷氨酰甘氨酸被去糖基化时，它被5-氧代脯氨酸取代。这些结果揭示了Botch通过去糖基化调节Notch信号传导，并确定了Notch的一种翻译后修饰，该修饰在神经发生中起重要作用。
Zotero 插件