Evidence map›Paper›PMID 26735921›Full record

ArticlePLoS pathogens2016

UIS2: A Unique Phosphatase Required for the Development of Plasmodium Liver Stages.

Min Zhang, Satish Mishra, Ramanavelan Sakthivel, Beatriz M A Fontoura, Victor Nussenzweig

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

28 citing papers in PubMed, 45 citations in OpenAlex.

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  9. Open biology · 2022
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  14. Transcriptional heterogeneity and tightly regulated changes in gene expression duringProceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  15. Protein Phosphatase PP2C Identification inBioMed research international · 2021
    Article
  16. Article
  17. Preparing for Transmission: Gene Regulation inFrontiers in cellular and infection microbiology · 2020
    Review
  18. 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 2 countries.

Min ZhangDepartment of Pathology, New York University School of Medicine, New York, New York, United States of America.
Satish MishraDivision of Parasitology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
Ramanavelan SakthivelDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
Beatriz M A FontouraDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
Victor NussenzweigDepartment of Pathology, New York University School of Medicine, New York, New York, United States of America.
New York University · USThe University of Texas Southwestern Medical Center · USCentral Drug Research Institute · IN

Funding

Using Chemical Biology to Interfere with the Influenza Virus Life CycleR01AI079110 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI FONTOURA, BEATRIZ MA, ROTH, MICHAEL G · 2010 to 2014
$2.0M
Solving the Artemisinin Dormancy ConundrumR21AI108592 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI NUSSENZWEIG, VICTOR · 2014 to 2015
$466k
NIAID NIH HHS AI108592NIAID NIH HHS R01 AI079110NIAID NIH HHS R01 AI079110-03NIAID NIH HHS R21 AI108592
6 · The paper itself

Abstract

Plasmodium salivary sporozoites are the infectious form of the malaria parasite and are dormant inside salivary glands of Anopheles mosquitoes. During dormancy, protein translation is inhibited by the kinase UIS1 that phosphorylates serine 59 in the eukaryotic initiation factor 2α (eIF2α). De-phosphorylation of eIF2α-P is required for the transformation of sporozoites into the liver stage. In mammalian cells, the de-phosphorylation of eIF2α-P is mediated by the protein phosphatase 1 (PP1). Using a series of genetically knockout parasites we showed that in malaria sporozoites, contrary to mammalian cells, the eIF2α-P phosphatase is a member of the PP2C/PPM phosphatase family termed UIS2. We found that eIF2α was highly phosphorylated in uis2 conditional knockout sporozoites. These mutant sporozoites maintained the crescent shape after delivery into mammalian host and lost their infectivity. Both uis1 and uis2 were highly transcribed in the salivary gland sporozoites but uis2 expression was inhibited by the Pumilio protein Puf2. The repression of uis2 expression was alleviated when sporozoites developed into liver stage. While most eukaryotic phosphatases interact transiently with their substrates, UIS2 stably bound to phosphorylated eIF2α, raising the possibility that high-throughput searches may identify chemicals that disrupt this interaction and prevent malaria infection.

Indexed as

AnimalsCell LineEukaryotic Initiation Factor-2Gene Knockout TechniquesHost-Parasite InteractionsHumansImmunoblottingImmunoprecipitationLife Cycle StagesMalariaMicePhosphoric Monoester HydrolasesPhosphorylationPlasmodium bergheiSporozoitesEukaryotic Initiation Factor-2Phosphoric Monoester Hydrolases

Identifiers

PMID26735921
PMCPMC4712141
OpenAlexW2266428623

What OpenQuestion holds

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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.