Evidence map›Paper›PMID 27210761›Full record

ArticleCell reports2016

Identification of a Paralog-Specific Notch1 Intracellular Domain Degron.

Matthew R Broadus, Tony W Chen, Leif R Neitzel, Victoria H Ng, Jeanne N Jodoin, Laura A Lee, Adrian Salic, David J Robbins, Anthony J Capobianco, James G Patton and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

10 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Fbxw7 is a driver of uterine carcinosarcoma by promoting epithelial-mesenchymal transition.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  6. Decoding the PTM-switchboard of Notch.Biochimica et biophysica acta. Molecular cell research · 2019
    Review
  7. Review
  8. Article
  9. Article
  10. Turn It Down a Notch.Frontiers in cell and developmental biology · 2016
    Review
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

12 authors at 7 institutions in 1 country.

Matthew R BroadusDepartment of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Tony W ChenDepartment of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Leif R NeitzelDepartment of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Victoria H NgDepartment of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Jeanne N JodoinDepartment of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Laura A LeeDepartment of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Adrian SalicDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
David J RobbinsMolecular Oncology Program, Division of Surgical Oncology, Dewitt Daughtry Family Department of Surgery, University of Miami, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Anthony J CapobiancoMolecular Oncology Program, Division of Surgical Oncology, Dewitt Daughtry Family Department of Surgery, University of Miami, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
James G PattonDepartment of Biological Sciences, Vanderbilt University, Nashville, TN 37232, USA.
Stacey S HuppertDivision of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Electronic address: stacey.huppert@cchmc.org.
Ethan LeeDepartment of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Ingram Cancer Center, Vanderbilt Medical Center, Nashville, TN 37232, USA. Electronic address: ethan.lee@vanderbilt.edu.
Vanderbilt University Medical Center · USHarvard University · USMolecular Oncology (United States) · USCincinnati Children's Hospital Medical Center · USMassachusetts Institute of Technology · USVanderbilt-Ingram Cancer CenterVanderbilt University · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
Integrated Biological Systems Training in OncologyT32CA119925 · NCI · VANDERBILT UNIVERSITY · PI Vivian Gama, William Patrick Tansey · 2008 to 2026
$7.6M
Training Program in Stem Cell and Regenerative Developmental BiologyT32HD007502 · NICHD · VANDERBILT UNIVERSITY · PI WRIGHT, CHRISTOPHER V · 1997 to 2022
$5.4M
MOLECULAR MECHANISMS OF NOTCH SIGNALING IN NEOPLASIAR01CA083736 · NCI · WISTAR INSTITUTE · PI CAPOBIANCO, ANTHONY JOHN · 2000 to 2016
$4.0M
Regulation of beta-catenin degradation during Wnt signal transductionR01GM081635 · NIGMS · VANDERBILT UNIVERSITY · PI LEE, ETHAN · 2007 to 2016
$2.4M
PDZ-dependent jagged 1 signaling in tumorigenesisR01CA125044 · NCI · WISTAR INSTITUTE · PI CAPOBIANCO, ANTHONY JOHN · 2008 to 2012
$1.6M
Mechanisms of Vertebrate Hedgehog SignalingR01GM092924 · NIGMS · HARVARD MEDICAL SCHOOL · PI SALIC, ADRIAN · 2011 to 2015
$1.6M
Molecular requirements for proliferation of fetal and adult liver progenitorsR01DK078640 · NIDDK · VANDERBILT UNIVERSITY · PI HUPPERT, STACEY S · 2008 to 2012
$1.5M
Novel mechanisms for oxysterols in cell-cell signalingR01GM110041 · NIGMS · HARVARD MEDICAL SCHOOL · PI SALIC, ADRIAN · 2014 to 2017
$1.4M
A newly discovered feed-forward mechanism controls photoreceptor fateR01EY024354 · NEI · VANDERBILT UNIVERSITY · PI PATTON, JAMES G. · 2014 to 2016
$1.3M
Role of ubiquitination in the Wnt pathwayR01GM103926 · NIGMS · VANDERBILT UNIVERSITY · PI LEE, ETHAN · 2013 to 2016
$1.2M
NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA083736NCI NIH HHS R01 CA125044NCI NIH HHS T32 CA119925NEI NIH HHS R01 EY024354NICHD NIH HHS T32 HD007502NIDDK NIH HHS R01 DK078640NIGMS NIH HHS R01 GM081635NIGMS NIH HHS R01 GM092924NIGMS NIH HHS R01 GM103926NIGMS NIH HHS R01 GM110041
6 · The paper itself

Abstract

Upon Notch pathway activation, the receptor is cleaved to release the Notch intracellular domain (NICD), which translocates to the nucleus to activate gene transcription. Using Xenopus egg extracts, we have identified a Notch1-specific destruction signal (N1-Box). We show that mutations in the N1-Box inhibit NICD1 degradation and that the N1-Box is transferable for the promotion of degradation of heterologous proteins in Xenopus egg extracts and in cultured human cells. Mutation of the N1-Box enhances Notch1 activity in cultured human cells and zebrafish embryos. Human cancer mutations within the N1-Box enhance Notch1 signaling in transgenic zebrafish, highlighting the physiological relevance of this destruction signal. We find that binding of the Notch nuclear factor, CSL, to the N1-Box blocks NICD1 turnover. Our studies reveal a mechanism by which degradation of NICD1 is regulated by the N1-Box to minimize stochastic flux and to establish a threshold for Notch1 pathway activation.

Indexed as

ProteolysisSequence Homology, Amino AcidAmino Acid SequenceAnimalsCell ExtractsEmbryo, NonmammalianF-Box ProteinsHEK293 CellsHumansMuscle ProteinsMutationProtein BindingProtein DomainsProtein StabilityReceptor, Notch1Regulatory Sequences, Nucleic AcidCell ExtractsF-Box ProteinsMuscle ProteinsReceptor, Notch1Ubiquitin-Protein Ligases

Identifiers

PMID27210761
PMCPMC4889555
OpenAlexW2399982540

What OpenQuestion holds

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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.