Evidence map›Paper›PMID 40183942›Full record

ArticleThe Journal of cell biology2025

The Abelson kinase and the Nedd4 family E3 ligases co-regulate Notch trafficking to limit signaling.

Julio Miranda-Alban, Nicelio Sanchez-Luege, Fernando M Valbuena, Chyan Rangel, Ilaria Rebay

Abstract read
In one paragraph

Article in The Journal of cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. 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

5 authors.

Julio Miranda-AlbanCommittee on Development, Regeneration, and Stem Cell Biology, University of Chicago , Chicago, IL, USA.ORCID 0009-0006-1094-7304
Nicelio Sanchez-LuegeCommittee on Development, Regeneration, and Stem Cell Biology, University of Chicago , Chicago, IL, USA.ORCID 0000-0002-3667-9639
Fernando M ValbuenaCell and Molecular Biology Graduate Program, University of Chicago , Chicago, IL, USA.ORCID 0000-0002-9236-1510
Chyan RangelBen May Department for Cancer Research, University of Chicago, Chicago, IL, USA.ORCID 0009-0003-5791-652X
Ilaria RebayCommittee on Development, Regeneration, and Stem Cell Biology, University of Chicago , Chicago, IL, USA.ORCID 0000-0002-2444-3864

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Precise output from the conserved Notch signaling pathway governs a plethora of cellular processes and developmental transitions. Unlike other pathways that use a cytoplasmic relay, the Notch cell surface receptor transduces signaling directly to the nucleus, with endocytic trafficking providing critical regulatory nodes. Here we report that the cytoplasmic tyrosine kinase Abelson (Abl) facilitates Notch internalization into late endosomes/multivesicular bodies (LEs), thereby limiting signaling output in both ligand-dependent and -independent contexts. Abl phosphorylates the PPxY motif within Notch, a molecular target for its degradation via Nedd4 family ubiquitin ligases. We show that Su(dx), a family member, mediates the Abl-directed LE regulation of Notch via the PPxY, while another family member, Nedd4Lo, contributes to Notch internalization into LEs through both PPxY-dependent and -independent mechanisms. Our findings demonstrate how a network of posttranslational modifiers converging at LEs cooperatively modulates Notch signaling to ensure the precision and robustness of its cellular and developmental functions.

Indexed as

Endosomal Sorting Complexes Required for TransportReceptors, NotchSignal TransductionUbiquitin-Protein LigasesAnimalsEndosomesHEK293 CellsHumansMiceNedd4 Ubiquitin Protein LigasesPhosphorylationProtein TransportRepressor ProteinsEndosomal Sorting Complexes Required for TransportNedd4L protein, humanNedd4 protein, humanNedd4 Ubiquitin Protein LigasesReceptors, NotchRepressor ProteinsUbiquitin-Protein Ligases

Identifiers

PMID40183942
PMCPMC11970431

What Socratic 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 Socratic graph.