Evidence map›Paper›PMID 38453365›Full record

ArticleLife science alliance2024

Oncogenic mutations of KRAS modulate its turnover by the CUL3/LZTR1 E3 ligase complex.

Andreas Damianou, Zhu Liang, Frederik Lassen, Iolanda Vendrell, George Vere, Svenja Hester, Philip D Charles, Adan Pinto-Fernandez, Alberto Santos, Roman Fischer and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Life science alliance, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Targeting WFS1 overcomes KRASNPJ precision oncology · 2026
    Article
  3. Article
  4. A cytoplasmic motif in HLA-E that drives clathrin-mediated endocytosis and VCP-associated postendocytic trafficking.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Review
  6. 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

11 authors.

Andreas DamianouTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK andreas.damianou@ndm.ox.ac.uk.ORCID 0000-0001-9383-5100
Zhu LiangTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Frederik LassenTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Iolanda VendrellTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID 0000-0001-7187-4061
George Vere
Svenja HesterTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Philip D CharlesTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Adan Pinto-FernandezTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Alberto SantosBig Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Roman FischerTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Benedikt M KesslerTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK benedikt.kessler@ndm.ox.ac.UK.ORCID 0000-0002-8160-2446

Funding

Medical Research Council G0501068
6 · The paper itself

Abstract

KRAS is a proto-oncogene encoding a small GTPase. Mutations contribute to ∼30% of human solid tumours, including lung adenocarcinoma, pancreatic, and colorectal carcinomas. Most KRAS activating mutations interfere with GTP hydrolysis, essential for its role as a molecular switch, leading to alterations in their molecular environment and oncogenic signalling. However, the precise signalling cascades these mutations affect are poorly understood. Here, APEX2 proximity labelling was used to profile the molecular environment of WT, G12D, G13D, and Q61H-activating KRAS mutants under starvation and stimulation conditions. Through quantitative proteomics, we demonstrate the presence of known KRAS interactors, including ARAF and LZTR1, which are differentially captured by WT and KRAS mutants. Notably, the KRAS mutations G12D, G13D, and Q61H abrogate their association with LZTR1, thereby affecting turnover. Elucidating the implications of LZTR1-mediated regulation of KRAS protein levels in cancer may offer insights into therapeutic strategies targeting KRAS-driven malignancies.

Indexed as

Colorectal NeoplasmsProto-Oncogene Proteins p21(ras)Ubiquitin-Protein LigasesCullin ProteinsHumansMutationSignal TransductionTranscription FactorsCUL3 protein, humanCullin ProteinsKRAS protein, humanLZTR1 protein, humanProto-Oncogene Proteins p21(ras)Transcription FactorsUbiquitin-Protein Ligases

Identifiers

PMID38453365
PMCPMC10921066

What Socratic holds

Textmetadata
LicenceCC BY
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.