Evidence map›Paper›PMID 25849741›Full record

ArticleNature communications2015

Quantitative analysis of the TNF-α-induced phosphoproteome reveals AEG-1/MTDH/LYRIC as an IKKβ substrate.

Ramesh K Krishnan, Hendrik Nolte, Tianliang Sun, Harmandeep Kaur, Krishnamoorthy Sreenivasan, Mario Looso, Stefan Offermanns, Marcus Krüger, Jakub M Swiercz

Abstract read
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
–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

40 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  9. International journal of biological sciences · 2025
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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

9 authors.

Ramesh K KrishnanDepartment of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
Hendrik NolteBiomolecular Mass Spectrometry, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
Tianliang SunDepartment of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
Harmandeep KaurDepartment of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
Krishnamoorthy SreenivasanDepartment of Cardiac Development and Remodelling, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
Mario LoosoBiomolecular Mass Spectrometry, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
Stefan Offermanns1] Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany [2] Medical Faculty, University of Frankfurt, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany.
Marcus KrügerBiomolecular Mass Spectrometry, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
Jakub M SwierczDepartment of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The inhibitor of the nuclear factor-κB (IκB) kinase (IKK) complex is a key regulator of the canonical NF-κB signalling cascade and is crucial for fundamental cellular functions, including stress and immune responses. The majority of IKK complex functions are attributed to NF-κB activation; however, there is increasing evidence for NF-κB pathway-independent signalling. Here we combine quantitative mass spectrometry with random forest bioinformatics to dissect the TNF-α-IKKβ-induced phosphoproteome in MCF-7 breast cancer cells. In total, we identify over 20,000 phosphorylation sites, of which ∼1% are regulated up on TNF-α stimulation. We identify various potential novel IKKβ substrates including kinases and regulators of cellular trafficking. Moreover, we show that one of the candidates, AEG-1/MTDH/LYRIC, is directly phosphorylated by IKKβ on serine 298. We provide evidence that IKKβ-mediated AEG-1 phosphorylation is essential for IκBα degradation as well as NF-κB-dependent gene expression and cell proliferation, which correlate with cancer patient survival in vivo.

Indexed as

Gene Expression Regulation, NeoplasticBlotting, WesternCell Adhesion MoleculesChromatin ImmunoprecipitationChromatography, LiquidHEK293 CellsHumansI-kappa B KinaseI-kappa B ProteinsImmunoprecipitationMass SpectrometryMCF-7 CellsMembrane ProteinsNF-kappa BNF-KappaB Inhibitor alphaPhosphoproteinsCell Adhesion MoleculesI-kappa B KinaseI-kappa B ProteinsIKBKB protein, humanMembrane ProteinsMTDH protein, humanNF-kappa BNF-KappaB Inhibitor alphaNFKBIA protein, humanPhosphoproteinsRNA-Binding ProteinsSerineTumor Necrosis Factor-alpha

Identifiers

PMID25849741
PMCPMC4396366

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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 OpenQuestion graph.