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

被引：31

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：

071013 [干细胞生物学];

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

[1]

Botch Promotes Neurogenesis by Antagonizing Notch [J].

Chi, Zhikai ;

Zhang, Jianmin ;

Tokunaga, Akinori ;

Harraz, Maged M. ;

Byrne, Sean T. ;

Dolinko, Andrew ;

Xu, Jing ;

Blackshaw, Seth ;

Gaiano, Nicholas ;

Dawson, Ted M. ;

Dawson, Valina L. .

DEVELOPMENTAL CELL, 2012, 22 (04) :707-720

[2]

Effects of S1 Cleavage on the Structure, Surface Export, and Signaling Activity of Human Notch1 and Notch2 [J].

Gordon, Wendy R. ;

Vardar-Ulu, Didem ;

L'Heureux, Sarah ;

Ashworth, Todd ;

Malecki, Michael J. ;

Sanchez-Irizarry, Cheryll ;

McArthur, Debbie G. ;

Histen, Gavin ;

Mitchell, Jennifer L. ;

Aster, Jon C. ;

Blacklow, Stephen C. .

PLOS ONE, 2009, 4 (08)

[3]

Selective Blockade of Transport via SERCA Inhibition: The Answer for Oncogenic Forms of Notch? [J].

Ilagan, Ma Xenia G. ;

Kopan, Raphael .

CANCER CELL, 2013, 23 (03) :267-269

[4]

Furin cleavage is not a requirement for Drosophila Notch function [J].

Kidd, S ;

Lieber, T .

MECHANISMS OF DEVELOPMENT, 2002, 115 (1-2) :41-51

[5]

Identification of Tubulin Deglutamylase among Caenorhabditis elegans and Mammalian Cytosolic Carboxypeptidases (CCPs) [J].

Kimura, Yoshishige ;

Kurabe, Nobuya ;

Ikegami, Koji ;

Tsutsumi, Koji ;

Konishi, Yoshiyuki ;

Kaplan, Oktay Ismail ;

Kunitomo, Hirofumi ;

Iino, Yuichi ;

Blacque, Oliver E. ;

Setou, Mitsutoshi .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (30) :22934-22939

[6]

The Canonical Notch Signaling Pathway: Unfolding the Activation Mechanism [J].

Kopan, Raphael ;

Ilagan, Ma. Xenia G. .

CELL, 2009, 137 (02) :216-233

[7]

Mammalian proapoptotic factor ChaC1 and its homologues function as γ-glutamyl cyclotransferases acting specifically on glutathione [J].

Kumar, Akhilesh ;

Tikoo, Shweta ;

Maity, Shuvadeep ;

Sengupta, Shantanu ;

Sengupta, Sagar ;

Kaur, Amandeep ;

Bachhawat, Anand Kumar .

EMBO REPORTS, 2012, 13 (12) :1095-1101

[8]

In Vivo Analysis of the Notch Receptor S1 Cleavage [J].

Lake, Robert J. ;

Grimm, Lisa M. ;

Veraksa, Alexey ;

Banos, Andrew ;

Artavanis-Tsakonas, Spyros .

PLOS ONE, 2009, 4 (08)

[9]

Giardia Duodenalis 14-3-3 Protein Is Polyglycylated by a Tubulin Tyrosine Ligase-like Member and Deglycylated by Two Metallocarboxypeptidases [J].

Lalle, Marco ;

Camerini, Serena ;

Cecchetti, Serena ;

Fantauzzi, Claudia Blasetti ;

Crescenzi, Marco ;

Pozio, Edoardo .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (06) :4471-4484

[10]

Notch signalling in vertebrate neural development [J].

Louvi, A ;

Artavanis-Tsakonas, S .

NATURE REVIEWS NEUROSCIENCE, 2006, 7 (02) :93-102

← 1 2 →