Evidence map›Paper›PMID 24767995›Full record

ArticleCell reports2014

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 and 4 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 35 citations in OpenAlex.

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  8. YTHDF2 destabilizes mRNA (New York, N.Y.) · 2020
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  15. ChaC2, an Enzyme for Slow Turnover of Cytosolic Glutathione.The Journal of biological chemistry · 2017
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Zhikai ChiNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Sean T ByrneNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Andrew DolinkoNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA.
Maged M HarrazNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA.
Min-Sik KimMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA.
George UmanahNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA.
Jun ZhongMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA.
Rong ChenNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA.
Jianmin ZhangNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Jinchong XuNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Li ChenNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA.
Akhilesh PandeyMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA; Department of Biological Chemistry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA; Department of Pathology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, 401 North Broadway, Baltimore, MD 21205, USA.
Ted M DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA. Electronic address: tdawson@jhmi.edu.
Valina L DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA. Electronic address: vdawson@jhmi.edu.
Johns Hopkins University · USJohns Hopkins Medicine · US

Funding

UNDERSTANDING NO SIGNALING RESULTING IN NEUROPROTECTION.P50DA000266 · NIDA · JOHNS HOPKINS UNIVERSITY · PI SNYDER, SOLOMON H. · 1985 to 2017
$45.2M
Understanding Mechanisms of a-synuclein pathologyP50NS038377 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KO, HANSEOK · 1998 to 2019
$38.8M
Mechanisms of Ischemic ToleranceR01NS040809 · NINDS · JOHNS HOPKINS UNIVERSITY · PI DAWSON, VALINA L. · 2001 to 2004
$1.5M
The Neuroprotective Gene Botch in Stroke-Induced NeurogenesisF31NS068010 · NINDS · JOHNS HOPKINS UNIVERSITY · PI BYRNE, SEAN T · 2010 to 2012
$125k
NIDA NIH HHS DA00266NIDA NIH HHS P50 DA000266NINDS NIH HHS 1F31NS068010NINDS NIH HHS NS40809NINDS NIH HHS P50 NS038377NINDS NIH HHS R01 NS040809
6 · The paper itself

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.

Indexed as

AnimalsBrainEmbryo, Mammaliangamma-GlutamylcyclotransferaseHEK293 CellsHumansMiceNeurogenesisProtein Structure, TertiaryReceptors, NotchRNA InterferenceRNA, Small InterferingSignal Transductiongamma-GlutamylcyclotransferaseGGCT protein, humanReceptors, NotchRNA, Small Interfering

Identifiers

PMID24767995
PMCPMC4031649
OpenAlexW2075135660

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.