Evidence map›Paper›PMID 25964327›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Inositol phosphate pathway controls transcription of telomeric expression sites in trypanosomes.

Igor Cestari, Ken Stuart

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

38 citing papers in PubMed, 56 citations in OpenAlex.

  1. Microbiology spectrum · 2026
    Article
  2. Article
  3. A factor integrating transcription and repression of surface antigen genes in African trypanosomes.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Regulation of Antigenic Variation byPathogens (Basel, Switzerland) · 2021
    Review
  13. Review
  14. The IPBiochimica et biophysica acta. Molecular cell research · 2021
    Review
  15. Article
  16. TheFrontiers in cellular and infection microbiology · 2021
    Article
  17. Review
  18. Review
  19. Review
  20. Review
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

2 authors at 1 institution in 1 country.

Igor CestariSeattle Biomedical Research Institute, Seattle, WA 98109; and.
Ken StuartSeattle Biomedical Research Institute, Seattle, WA 98109; and Department of Global Health, University of Washington, Seattle, WA 98195 ken.stuart@seattlebiomed.org.
Center for Infectious Disease Research · US

Funding

MITOCHONDRIAL DNA OF NORMAL AND MUTANT TRYPANOSOMESR01AI014102 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI KENNETH D STUART · 1985 to 2026
$20.9M
Genome wide assessment of essential genes in Trypanosoma bruceiR01AI078962 · NIAID · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI STUART, KENNETH D · 2010 to 2012
$2.5M
NIAID NIH HHS R01 AI014102NIAID NIH HHS R01AI014102-37S1NIAID NIH HHS R01 AI078962NIAID NIH HHS R01AI078962
6 · The paper itself

Abstract

African trypanosomes evade clearance by host antibodies by periodically changing their variant surface glycoprotein (VSG) coat. They transcribe only one VSG gene at a time from 1 of about 20 telomeric expression sites (ESs). They undergo antigenic variation by switching transcription between telomeric ESs or by recombination of the VSG gene expressed. We show that the inositol phosphate (IP) pathway controls transcription of telomeric ESs and VSG antigenic switching in Trypanosoma brucei. Conditional knockdown of phosphatidylinositol 5-kinase (TbPIP5K) or phosphatidylinositol 5-phosphatase (TbPIP5Pase) or overexpression of phospholipase C (TbPLC) derepresses numerous silent ESs in T. brucei bloodstream forms. The derepression is specific to telomeric ESs, and it coincides with an increase in the number of colocalizing telomeric and RNA polymerase I foci in the nucleus. Monoallelic VSG transcription resumes after reexpression of TbPIP5K; however, most of the resultant cells switched the VSG gene expressed. TbPIP5K, TbPLC, their substrates, and products localize to the plasma membrane, whereas TbPIP5Pase localizes to the nucleus proximal to telomeres. TbPIP5Pase associates with repressor/activator protein 1 (TbRAP1), and their telomeric silencing function is altered by TbPIP5K knockdown. These results show that specific steps in the IP pathway control ES transcription and antigenic switching in T. brucei by epigenetic regulation of telomere silencing.

Indexed as

Amino Acid SequenceAnimalsAntigenic VariationGene Knockdown TechniquesGenes, ProtozoanGenes, SwitchHumansInositol PhosphatesMetabolic Networks and PathwaysMolecular Sequence DataPhosphoinositide 5-PhosphatasesPhosphoric Monoester HydrolasesPhosphotransferases (Alcohol Group Acceptor)Protozoan ProteinsSequence Homology, Amino AcidTelomere1-phosphatidylinositol-4-phosphate 5-kinaseInositol PhosphatesPhosphoinositide 5-PhosphatasesPhosphoric Monoester HydrolasesPhosphotransferases (Alcohol Group Acceptor)Protozoan ProteinsVariant Surface Glycoproteins, Trypanosomaantigenic variationinositol phosphatestelomere silencingtranscriptiontrypanosomes

Identifiers

PMID25964327
PMCPMC4450425
OpenAlexW1576894338

What OpenQuestion holds

Textmetadata
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.