Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch

Zhikai Chi, Sean T. Byrne, Andrew Dolinko, Maged M. Harraz, Min Sik Kim, George Umanah, Jun Zhong, Rong Chen, Jianmin Zhang, Jinchong Xu, Li Chen, Akhilesh Pandey, Ted M. Dawson, Valina L. Dawson

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)681-688
Number of pages8
JournalCell reports
Volume7
Issue number3
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Furin
Neurogenesis
Biochemical Phenomena
Post Translational Protein Processing
Proline
Glycine
Glutamic Acid
Carbon
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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

Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch. / 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.

In: Cell reports, Vol. 7, No. 3, 01.01.2014, p. 681-688.

Research output: Contribution to journalArticle

Chi, Z, Byrne, ST, Dolinko, A, Harraz, MM, Kim, MS, Umanah, G, Zhong, J, Chen, R, Zhang, J, Xu, J, Chen, L, Pandey, A, Dawson, TM & Dawson, VL 2014, 'Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch', Cell reports, vol. 7, no. 3, pp. 681-688. https://doi.org/10.1016/j.celrep.2014.03.048
Chi Z, Byrne ST, Dolinko A, Harraz MM, Kim MS, Umanah G et al. Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch. Cell reports. 2014 Jan 1;7(3):681-688. https://doi.org/10.1016/j.celrep.2014.03.048
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. / Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch. In: Cell reports. 2014 ; Vol. 7, No. 3. pp. 681-688.
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