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

被引：28

作者：

Chi, Zhikai ^{[1
,2
,3
]}

Byrne, Sean T. ^{[1
,2
,4
]}

Dolinko, Andrew ^{[1
,2
]}

Harraz, Maged M. ^{[1
,2
]}

Kim, Min-Sik ^{[5
]}

Umanah, George ^{[1
,2
]}

Zhong, Jun ^{[5
]}

Chen, Rong ^{[1
,2
]}

Zhang, Jianmin ^{[1
,2
,9
]}

Xu, Jinchong ^{[1
,2
,9
]}

Chen, Li ^{[1
,2
]}

Pandey, Akhilesh ^{[5
,6
,7
,8
]}

Dawson, Ted M. ^{[1
,2
,3
,9
,10
]}

Dawson, Valina L. ^{[1
,2
,3
,4
,9
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Neuroregenerat Program, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Stem Cell Program, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA

[7] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

[8] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[9] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[10] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

来源：

CELL REPORTS | 2014年 / 7卷 / 03期

关键词：

IDENTIFICATION; CLEAVAGE; PROMOTES; PROTEIN; TUBULIN; ENZYME; FURIN; VIVO;

D O I：

10.1016/j.celrep.2014.03.048

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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

引用

页码：681 / 688

页数：8

共 20 条

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