Evidence map›Paper›PMID 21994942›Full record

ArticleThe Journal of biological chemistry2011

MAPKKK-independent regulation of the Hog1 stress-activated protein kinase in Candida albicans.

Jill Cheetham, Donna M MacCallum, Kathryn S Doris, Alessandra da Silva Dantas, Susan Scorfield, Frank Odds, Deborah A Smith, Janet Quinn

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. 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
1.6field-weighted citation impact, top 19% 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, 47 citations in OpenAlex.

  1. A roadmap to chemically reactive species: how diverse oxidants affectMicrobiology and molecular biology reviews : MMBR · 2025
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  8. Immune cells fold and damage fungal hyphae.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  9. Adaptation to Endoplasmic Reticulum Stress inFrontiers in microbiology · 2021
    Article
  10. Protein-Protein Interactions inFrontiers in microbiology · 2019
    Review
  11. Stress-Activated Protein Kinases in Human Fungal Pathogens.Frontiers in cellular and infection microbiology · 2019
    Review
  12. Article
  13. Article
  14. Article
  15. Non-canonical Activities of Hog1 Control Sensitivity ofFrontiers in cellular and infection microbiology · 2018
    Article
  16. PbsB Regulates Morphogenesis, Aflatoxin B1 Biosynthesis, and Pathogenicity ofFrontiers in cellular and infection microbiology · 2018
    Article
  17. Article
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  19. Article
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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

8 authors at 2 institutions in 1 country.

Jill CheethamInstitute for Cell and Molecular Biosciences, Faculty of Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom.
Donna M MacCallumAberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.
Kathryn S DorisInstitute for Cell and Molecular Biosciences, Faculty of Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom.
Alessandra da Silva DantasInstitute for Cell and Molecular Biosciences, Faculty of Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom.
Susan ScorfieldInstitute for Cell and Molecular Biosciences, Faculty of Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom.
Frank OddsAberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.
Deborah A SmithInstitute for Cell and Molecular Biosciences, Faculty of Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom.
Janet QuinnInstitute for Cell and Molecular Biosciences, Faculty of Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom. Electronic address: janet.quinn@ncl.ac.uk.
Newcastle University · GBUniversity of Aberdeen · GB

Funding

Biotechnology and Biological Sciences Research CouncilWellcome Trust
6 · The paper itself

Abstract

The Hog1 stress-activated protein kinase regulates both stress responses and morphogenesis in Candida albicans and is essential for the virulence of this major human pathogen. Stress-induced Hog1 phosphorylation is regulated by the upstream MAPKK, Pbs2, which in turn is regulated by the MAPKKK, Ssk2. Here, we have investigated the role of phosphorylation of Hog1 and Pbs2 in Hog1-mediated processes in C. albicans. Mutation of the consensus regulatory phosphorylation sites of Hog1 (Thr-174/Tyr-176) and Pbs2 (Ser-355/Thr-359), to nonphosphorylatable residues, resulted in strains that phenocopied hog1Δ and pbs2Δ cells. Consistent with this, stress-induced phosphorylation of Hog1 was abolished in cells expressing nonphosphorylatable Pbs2 (Pbs2(AA)). However, mutation of the consensus sites of Pbs2 to phosphomimetic residues (Pbs2(DD)) failed to constitutively activate Hog1. Furthermore, Ssk2-independent stress-induced Hog1 activation was observed in Pbs2(DD) cells. Collectively, these data reveal a previously uncharacterized MAPKKK-independent mechanism of Hog1 activation in response to stress. Although Pbs2(DD) cells did not exhibit high basal levels of Hog1 phosphorylation, overexpression of an N-terminal truncated form of Ssk2 did result in constitutive Hog1 activation, which was further increased upon stress. Significantly, both Pbs2(AA) and Pbs2(DD) cells displayed impaired stress resistance and attenuated virulence in a mouse model of disease, whereas only Pbs2(AA) cells exhibited the morphological defects associated with loss of Hog1 function. This indicates that Hog1 mediates C. albicans virulence by conferring stress resistance rather than regulating morphogenesis.

Indexed as

Gene Expression Regulation, EnzymologicGene Expression Regulation, FungalAllelesAnimalsBacterial ProteinsCandida albicansDisease Models, AnimalFemaleMAP Kinase Kinase KinasesMiceMice, Inbred BALB CMitogen-Activated Protein Kinase 8Mitogen-Activated Protein KinasesMutagenesisMutationOsmosisBacterial ProteinsHOG1 protein, S cerevisiaeMAP Kinase Kinase KinasesMitogen-Activated Protein Kinase 8Mitogen-Activated Protein KinasesProtein KinasesSaccharomyces cerevisiae Proteins

Identifiers

PMID21994942
PMCPMC3234903
OpenAlexW2023192033

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.