Evidence map›Paper›PMID 25105836›Full record

ArticleMetabolites2014

The Succinated Proteome of FH-Mutant Tumours.

Ming Yang, Nicola Ternette, Huizhong Su, Raliat Dabiri, Benedikt M Kessler, Julie Adam, Bin Tean Teh, Patrick J Pollard

Open access · goldAbstract read
In one paragraph

Article in Metabolites, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

31 citing papers in PubMed, 59 citations in OpenAlex.

  1. Review
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  10. Article
  11. Article
  12. Review
  13. Review
  14. Oncometabolites in renal cancer.Nature reviews. Nephrology · 2020
    Review
  15. Article
  16. Succination of Protein Thiols in Human Brain Aging.Frontiers in aging neuroscience · 2020
    Review
  17. Identification of bioactive metabolites using activity metabolomics.Nature reviews. Molecular cell biology · 2019
    Review
  18. Review
  19. Article
  20. Biochemical characterization and essentiality ofThe Journal of biological chemistry · 2018
    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

8 authors at 5 institutions in 2 countries.

Ming YangCancer Biology and Metabolism Group, Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UK. ming.yang@igmm.ed.ac.uk.
Nicola TernetteCentral Proteomics Facility, Target Discovery Institute, University of Oxford, Oxford OX3 7FZ, UK. nicola.ternette@ndm.ox.ac.uk.
Huizhong SuCancer Biology and Metabolism Group, Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UK. huizhong.su@igmm.ed.ac.uk.
Raliat DabiriCancer Biology and Metabolism Group, Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UK. rd292@exeter.ac.uk.
Benedikt M KesslerCentral Proteomics Facility, Target Discovery Institute, University of Oxford, Oxford OX3 7FZ, UK. benedikt.kessler@ndm.ox.ac.uk.
Julie AdamOxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford OX3 7LJ, UK. julie.adam@ocdem.ox.ac.uk.
Bin Tean TehCancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, #12-01,117599, Singapore. teh.bin.tean@singhealth.com.sg.
Patrick J PollardCancer Biology and Metabolism Group, Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UK. patrick.pollard@igmm.ed.ac.uk.
Edinburgh Cancer Research · GBOxford Policy Management · GBNational University of Singapore · SGOxford Centre for Diabetes, Endocrinology and Metabolism · GBWestern General Hospital · GB

Funding

Cancer Research UK A13349European Research Council 310837
6 · The paper itself

Abstract

Inherited mutations in the Krebs cycle enzyme fumarate hydratase (FH) predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC). Loss of FH activity in HLRCC tumours causes accumulation of the Krebs cycle intermediate fumarate to high levels, which may act as an oncometabolite through various, but not necessarily mutually exclusive, mechanisms. One such mechanism, succination, is an irreversible non-enzymatic modification of cysteine residues by fumarate, to form S-(2-succino)cysteine (2SC). Previous studies have demonstrated that succination of proteins including glyceraldehyde 3-phosphate dehydrogenase (GAPDH), kelch-like ECH-associated protein 1 (KEAP1) and mitochondrial aconitase (ACO2) can have profound effects on cellular metabolism. Furthermore, immunostaining for 2SC is a sensitive and specific biomarker for HLRCC tumours. Here, we performed a proteomic screen on an FH-mutant tumour and two HLRCC-derived cancer cell lines and identified 60 proteins where one or more cysteine residues were succinated; 10 of which were succinated at cysteine residues either predicted, or experimentally proven, to be functionally significant. Bioinformatic enrichment analyses identified most succinated targets to be involved in redox signaling. To our knowledge, this is the first proteomic-based succination screen performed in human tumours and cancer-derived cells and has identified novel 2SC targets that may be relevant to the pathogenesis of HLRCC.

Identifiers

PMID25105836
PMCPMC4192685
OpenAlexW2141526363

What OpenQuestion 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 OpenQuestion graph.