Evidence map›Paper›PMID 26492041›Full record

ArticlePLoS pathogens2015

Modulation of the Surface Proteome through Multiple Ubiquitylation Pathways in African Trypanosomes.

Martin Zoltner, Ka Fai Leung, Sam Alsford, David Horn, Mark C Field

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

30 citing papers in PubMed, 48 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Targeted protein degradation might present a novel therapeutic approach in the fight against African trypanosomiasis.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2023
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. 100 Years of Suramin.Antimicrobial agents and chemotherapy · 2020
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Martin ZoltnerDivision of Biological Chemistry and Drug Discovery, University of Dundee, Dundee, United Kingdom.
Ka Fai LeungDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Sam AlsfordLondon School of Hygiene and Tropical Medicine, Keppel Street, London, United Kingdom.
David HornDivision of Biological Chemistry and Drug Discovery, University of Dundee, Dundee, United Kingdom.
Mark C FieldDivision of Biological Chemistry and Drug Discovery, University of Dundee, Dundee, United Kingdom.
University of Dundee · GBLondon School of Hygiene & Tropical Medicine · GBUniversity of Cambridge · GB

Funding

Medical Research Council MR/K000500/1Medical Research Council MR/K008749/1Medical Research Council MR/K008749/2Wellcome Trust 100320
6 · The paper itself

Abstract

Recently we identified multiple suramin-sensitivity genes with a genome wide screen in Trypanosoma brucei that includes the invariant surface glycoprotein ISG75, the adaptin-1 (AP-1) complex and two deubiquitylating enzymes (DUBs) orthologous to ScUbp15/HsHAUSP1 and pVHL-interacting DUB1 (type I), designated TbUsp7 and TbVdu1, respectively. Here we have examined the roles of these genes in trafficking of ISG75, which appears key to suramin uptake. We found that, while AP-1 does not influence ISG75 abundance, knockdown of TbUsp7 or TbVdu1 leads to reduced ISG75 abundance. Silencing TbVdu1 also reduced ISG65 abundance. TbVdu1 is a component of an evolutionarily conserved ubiquitylation switch and responsible for rapid receptor modulation, suggesting similar regulation of ISGs in T. brucei. Unexpectedly, TbUsp7 knockdown also blocked endocytosis. To integrate these observations we analysed the impact of TbUsp7 and TbVdu1 knockdown on the global proteome using SILAC. For TbVdu1, ISG65 and ISG75 are the only significantly modulated proteins, but for TbUsp7 a cohort of integral membrane proteins, including the acid phosphatase MBAP1, that is required for endocytosis, and additional ISG-related proteins are down-regulated. Furthermore, we find increased expression of the ESAG6/7 transferrin receptor and ESAG5, likely resulting from decreased endocytic activity. Therefore, multiple ubiquitylation pathways, with a complex interplay with trafficking pathways, control surface proteome expression in trypanosomes.

Indexed as

UbiquitinationClathrinEndocytosisMembrane GlycoproteinsProteomeProtozoan ProteinsSuraminTranscription Factor AP-1Trypanosoma brucei bruceiClathrinISG65 protein, Trypanosoma bruceiISG75 protein, Trypanosoma bruceiMembrane GlycoproteinsProteomeProtozoan ProteinsSuraminTranscription Factor AP-1

Identifiers

PMID26492041
PMCPMC4619645
OpenAlexW2127815120

What OpenQuestion holds

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Read underepoch 390

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.