Evidence mapPaperPMID 41884348Full record

ReviewFrontiers in molecular biosciences2026

E3 ubiquitin ligases: structural diversity, dysregulation in disease, and their emerging role in targeted therapeutic strategies.

Srineevas Sriram, Prahalad Krishnakumar, C Sudandiradoss

Abstract readReview
In one paragraph

Review in Frontiers in molecular biosciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

3 authors.

Srineevas SriramDepartment of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Prahalad KrishnakumarDepartment of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
C SudandiradossDepartment of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Ubiquitin-Proteasome System (UPS) is a key mechanism of cellular homeostasis. A central part of this mechanism is E3 ubiquitin ligases, which selectively direct proteins to be ubiquitinated for degradation via the UPS. In this review we give an integrated overview of the classification, structural and the functional characteristics of the main families of E3 ligases, i.e., RING, HECT, RBR and RCR E3 ligases, as well as non-canonical ligase families. Furthermore, we describe how these ligases contribute to several important biological processes like proteostasis, DNA-repair, cell-cycle control, immune-regulation and neurodegeneration. Here we present examples of diseases that occur due to abnormal functioning of E3 ligases (e.g., cancers, neurodegenerative diseases and immune dysfunctions). Finally, the review also covers emerging therapeutic strategies based on E3 ligases with an emphasis on proteolysis-targeting chimeras (PROTACs) and the use of E3 ligase-modulatory approaches to improve CAR-T-cell-based immunotherapies. Recent developments in artificial intelligence and machine learning have already transformed E3-ligase research through the possibility of high-throughput ligand screening, structure-function prediction and rational design of degraders. Our review aims to integrate our knowledge of E3 ligases and show how converging biochemistry, immunotherapy and AI-driven research can lead to novel precision strategies for targeted protein degradation.

Indexed as

AICAR t cellE3 ligasesPROTACsproteostasistherapeuticsubiquitination

Identifiers

PMID41884348
PMCPMC13008643

What Socratic holds

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Registered trials

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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.