Evidence map›Paper›PMID 37527352›Full record

ArticleScience signaling2023

A spatiotemporal Notch interaction map from plasma membrane to nucleus.

Alexandre P Martin, Gary A Bradshaw, Robyn J Eisert, Emily D Egan, Lena Tveriakhina, Julia M Rogers, Andrew N Dates, Gustavo Scanavachi, Jon C Aster, Tom Kirchhausen and 2 more

Open access · greenAbstract read
In one paragraph

Article in Science signaling, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

16 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Notch2 Directs aTreg Cell Fate Toward Immunoregulation or Inflammatory Pyroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Understanding the role of NOTCH2 mutation in centronuclear myopathy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
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 4 institutions in 1 country.

Alexandre P MartinDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-3875-6754
Gary A BradshawDepartment of Systems Biology, Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-9724-6100
Robyn J EisertDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-7977-249X
Emily D EganDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-9819-8403
Lena TveriakhinaDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-8659-8207
Julia M RogersDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Andrew N DatesDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Gustavo ScanavachiDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-4001-3389
Jon C AsterDepartment of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Tom KirchhausenDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-0559-893X
Marian KalocsayDepartment of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-4187-5829
Stephen C BlacklowDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-6904-1981
Harvard University · USBoston Children's Hospital · USBrigham and Women's Hospital · USThe University of Texas MD Anderson Cancer Center · US

Funding

The Harvard Clinical and Translational Science CenterUL1TR002541 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2018 to 2022
$93.0M
Notch Signaling in CancerR35CA220340 · NCI · HARVARD MEDICAL SCHOOL · PI BLACKLOW, STEPHEN C. · 2017 to 2023
$7.1M
VISUALIZATION OF SUBCELLULAR DYNAMICS IN MULTICELLULAR ORGANISMSR35GM130386 · NIGMS · BOSTON CHILDREN'S HOSPITAL · PI TOMAS KIRCHHAUSEN · 2019 to 2026
$4.0M
Dynamics of Notch SignalingR01CA272484 · NCI · HARVARD MEDICAL SCHOOL · PI Stephen C. Blacklow · 2022 to 2026
$3.3M
Dynamic mechanisms of transcriptional coactivator function in Notch signalingK99GM144750 · NIGMS · HARVARD MEDICAL SCHOOL · PI ROGERS, JULIA MARIA · 2022 to 2023
$222k
NCATS NIH HHS UL1 TR002541NCI NIH HHS R01 CA272484NCI NIH HHS R35 CA220340NIGMS NIH HHS K99 GM144750NIGMS NIH HHS R35 GM130386
6 · The paper itself

Abstract

Notch signaling relies on ligand-induced proteolysis of the transmembrane receptor Notch to liberate a nuclear effector that drives cell fate decisions. Upon ligand binding, sequential cleavage of Notch by the transmembrane protease ADAM10 and the intracellular protease γ-secretase releases the Notch intracellular domain (NICD), which translocates to the nucleus and forms a complex that induces target gene transcription. To map the location and timing of the individual steps required for the proteolysis and movement of Notch from the plasma membrane to the nucleus, we used proximity labeling with quantitative, multiplexed mass spectrometry to monitor the interaction partners of endogenous NOTCH2 after ligand stimulation in the presence of a γ-secretase inhibitor and as a function of time after inhibitor removal. Our studies showed that γ-secretase-mediated cleavage of NOTCH2 occurred in an intracellular compartment and that formation of nuclear complexes and recruitment of chromatin-modifying enzymes occurred within 45 min of inhibitor washout. These findings provide a detailed spatiotemporal map tracking the path of Notch from the plasma membrane to the nucleus and identify signaling events that are potential targets for modulating Notch activity.

Indexed as

Amyloid Precursor Protein SecretasesReceptors, NotchCell MembraneLigandsReceptor, Notch1Signal TransductionAmyloid Precursor Protein SecretasesLigandsReceptor, Notch1Receptors, Notch

Identifiers

PMID37527352
PMCPMC10560377
OpenAlexW4385451088

What Socratic holds

Textmetadata
LicenceTDM
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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 Socratic graph.