Evidence map›Paper›PMID 24129246›Full record

ArticleBritish journal of cancer2013

SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1.

H Zhang, Y Xu, A Filipovic, L C Lit, C-Y Koo, J Stebbing, G Giamas

Open access · hybridAbstract read
In one paragraph

Article in British journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

15 citing papers in PubMed, 18 citations in OpenAlex.

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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

7 authors at 2 institutions in 2 countries.

H ZhangDivision of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 ONN, UK.
Y Xu
A Filipovic
L C Lit
C-Y Koo
J Stebbing
G Giamas
Hammersmith Hospital · GBImperial College London · GB

Funding

Cancer Research UK 14549Department of Health NIHR-RP-011-053Medical Research Council G1100425Medical Research Council MR/L000172/1
6 · The paper itself

Abstract

backgroundWe have previously identified kinase suppressor of ras-1 (KSR1) as a potential regulatory gene in breast cancer. KSR1, originally described as a novel protein kinase, has a role in activation of mitogen-activated protein kinases. Emerging evidence has shown that KSR1 may have dual functions as an active kinase as well as a scaffold facilitating multiprotein complex assembly. Although efforts have been made to study the role of KSR1 in certain tumour types, its involvement in breast cancer remains unknown.

methodsA quantitative mass spectrometry analysis using stable isotope labelling of amino acids in cell culture (SILAC) was implemented to identify KSR1-regulated phosphoproteins in breast cancer. In vitro luciferase assays, co-immunoprecipitation as well as western blotting experiments were performed to further study the function of KSR1 in breast cancer.

resultsOf significance, proteomic analysis reveals that KSR1 overexpression decreases deleted in breast cancer-1 (DBC1) phosphorylation. Furthermore, we show that KSR1 decreases the transcriptional activity of p53 by reducing the phosphorylation of DBC1, which leads to a reduced interaction of DBC1 with sirtuin-1 (SIRT1); this in turn enables SIRT1 to deacetylate p53.

conclusionOur findings integrate KSR1 into a network involving DBC1 and SIRT1, which results in the regulation of p53 acetylation and its transcriptional activity.

Indexed as

Adaptor Proteins, Signal TransducingAmino AcidsBreast NeoplasmsCell Culture TechniquesDown-RegulationFemaleGene Expression Regulation, NeoplasticHCT116 CellsHumansIsotope LabelingPhosphoproteinsProtein KinasesProteomicsSirtuin 1Transcriptional ActivationTumor Cells, CulturedAdaptor Proteins, Signal TransducingAmino AcidsCCAR2 protein, humanKSR-1 protein kinasePhosphoproteinsProtein KinasesSIRT1 protein, humanSirtuin 1TP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID24129246
PMCPMC3833216
OpenAlexW2089042565

What OpenQuestion holds

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LicenceCC BY-NC-SA
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.