Evidence map›Paper›PMID 38511488›Full record

ArticleProtein science : a publication of the Protein Society2024

Unraveling paralog-specific Notch signaling through thermodynamics of ternary complex formation and transcriptional activation of chimeric receptors.

Kristen M Ramsey, Doug Barrick

Open access · bronzeAbstract read
In one paragraph

Article in Protein science : a publication of the Protein Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.4field-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

8 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
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  7. Modes of Notch signalling in development and disease.Nature reviews. Molecular cell biology · 2025
    Review
  8. 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

2 authors at 1 institution in 1 country.

Kristen M RamseyT.C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland, USA.ORCID 0000-0002-9974-4274
Doug BarrickT.C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland, USA.ORCID 0000-0001-7291-1389
Johns Hopkins University · US

Funding

REPEAT-PROTEINS;STABILITY, FOLDING KINETICS &EVOLUTIONR01GM068462 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI BARRICK, DOUGLAS E. · 2005 to 2025
$6.3M
Structure And Mechanism In Intracellular Notch SignalingR01GM060001 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI BARRICK, DOUGLAS E. · 2001 to 2015
$3.6M
The Identity of the Notch Ankyrin Repeat Domain as a Determinant of Isoform-Specific Notch SignalingF32CA260117 · NCI · JOHNS HOPKINS UNIVERSITY · PI RAMSEY, KRISTEN MICHELLE · 2021 to 2023
$210k
NCI NIH HHS F32 CA260117NIGMS NIH HHS R01 GM060001NIGMS NIH HHS R01 GM068462NIH HHS 1R01-GM068462
6 · The paper itself

Abstract

Notch signaling in humans is mediated by four paralogous receptors that share conserved architectures and possess overlapping, yet non-redundant functions. The receptors share a canonical activation pathway wherein upon extracellular ligand binding, the Notch intracellular domain (NICD) is cleaved from the membrane and translocates to the nucleus where its N-terminal RBP-j-associated molecule (RAM) region and ankyrin repeat (ANK) domain bind transcription factor CSL and recruit co-activator Mastermind-like-1 (MAML1) to activate transcription. However, different paralogs can lead to distinct outcomes. To better understand paralog-specific differences in Notch signaling, we performed a thermodynamic analysis of the Notch transcriptional activation complexes for all four Notch paralogs using isothermal titration calorimetry. Using chimeric constructs, we find that the RAM region is the primary determinant of stability of binary RAMANK:CSL complexes, and that the ANK regions are largely the determinants of MAML1 binding to pre-formed RAMANK:CSL complexes. Free energies of these binding reactions (ΔG

Indexed as

Gene Expression RegulationReceptors, NotchDNA-Binding ProteinsHumansProtein BindingThermodynamicsTranscriptional ActivationTranscription FactorsDNA-Binding ProteinsMAML1 protein, humanReceptors, NotchTranscription Factorsisothermal titration calorimetryNotch paralogsNotch signalingprotein–protein interactionstranscriptional activation

Identifiers

PMID38511488
PMCPMC10962485
OpenAlexW4393055313

What OpenQuestion holds

Textmetadata
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.