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Botch is a ?-glutamyl cyclotransferase that deglycinates and antagonizes Notch.

ABSTRACT: 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 ?-glutamyl cyclotransferase (GGCT) activity that deglycinates Notch, which prevents the S1 furin-like cleavage. Moreover, Notch is monoglycinated on the ?-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 ?-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.

SUBMITTER: Chi Z

PROVIDER: S-EPMC4031649 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Botch is a γ-glutamyl cyclotransferase that deglycinates and antagonizes Notch.

Chi Zhikai Z Byrne Sean T ST Dolinko Andrew A Harraz Maged M MM Kim Min-Sik MS Umanah George G Zhong Jun J Chen Rong R Zhang Jianmin J Xu Jinchong J Chen Li L Pandey Akhilesh A Dawson Ted M TM Dawson Valina L VL

Cell reports 20140424 3

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 ...[more]

PMID: 24767995

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