Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch
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 prev...
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| Format: | Article |
| Language: | English |
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Elsevier
2014-05-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714002459 |
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doaj-9faf84c02be24fce9a24f5832203ce302020-11-25T01:13:36ZengElsevierCell Reports2211-12472014-05-017368168810.1016/j.celrep.2014.03.048Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes NotchZhikai Chi0Sean T. Byrne1Andrew Dolinko2Maged M. Harraz3Min-Sik Kim4George Umanah5Jun Zhong6Rong Chen7Jianmin Zhang8Jinchong Xu9Li Chen10Akhilesh Pandey11Ted M. Dawson12Valina L. Dawson13Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USAMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USAMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USAMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USABotch 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.http://www.sciencedirect.com/science/article/pii/S2211124714002459 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch Cell Reports |
| author_facet |
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 |
| author_sort |
Zhikai Chi |
| title |
Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch |
| title_short |
Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch |
| title_full |
Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch |
| title_fullStr |
Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch |
| title_full_unstemmed |
Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch |
| title_sort |
botch is a γ-glutamyl cyclotransferase that deglycinates and antagonizes notch |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2014-05-01 |
| description |
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. |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124714002459 |
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