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. © 2014 The Authors.
Chi, Z., Byrne, S. T., Dolinko, A., Harraz, M. M., Kim, M. S., Umanah, G., … Dawson, V. L. (2014). Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch. Cell Reports, 7(3), 681–688. https://doi.org/10.1016/j.celrep.2014.03.048