Evidence map›Paper›PMID 25525876›Full record

ArticleCell2014

Dual proteolytic pathways govern glycolysis and immune competence.

Wei Lu, Yu Zhang, David O McDonald, Huie Jing, Bernadette Carroll, Nic Robertson, Qian Zhang, Helen Griffin, Sharon Sanderson, Jeremy H Lakey and 16 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing 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

34 citing papers in PubMed, 63 citations in OpenAlex.

  1. Celiac disease and developmental delay as the first manifestations of tripeptidyl peptidase 2 deficiency.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026
    Article
  2. Review
  3. Review
  4. Human immunity.Journal of human immunity · 2025
    Article
  5. Article
  6. Nucleotide metabolism, leukodystrophies, and CNS pathology.Journal of inherited metabolic disease · 2024
    Review
  7. Article
  8. Article
  9. Proteostasis in T cell aging.Seminars in immunology · 2023
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Dysfunction of chaperone-mediated autophagy in human diseases.Molecular and cellular biochemistry · 2021
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. 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

26 authors at 8 institutions in 4 countries.

Wei LuLaboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; NIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD 20892, USA.
Yu ZhangLaboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; NIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD 20892, USA.
David O McDonaldInstitute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Huie JingLaboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; NIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD 20892, USA.
Bernadette CarrollInstitute of Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Nic RobertsonInstitute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK.
Qian ZhangLaboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; NIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD 20892, USA.
Helen GriffinInstitute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
Sharon SandersonNIHR BRC Translational Immunology Lab, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.
Jeremy H LakeyInstitute of Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Neil V MorganCentre for Cardiovascular Sciences, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Louise N ReynardInstitute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Lixin ZhengLaboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; NIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD 20892, USA.
Heardley M MurdockNIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD 20892, USA; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Stuart E TurveyDepartment of Pediatrics, Child & Family Research Institute and BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.
Scott J HackettPaediatric Immunology Department, Birmingham Heartlands Hospital, Birmingham B9 5SS, UK.
Tim PrestidgeBlood and Cancer Center, Starship Children's Hospital, Auckland 1142, New Zealand.
Julie M HallGreat North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK.
Andrew J CantInstitute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK.
Helen F MatthewsLaboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; NIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD 20892, USA.
Mauro F Santibanez KorefInstitute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
Anna Katharina SimonNIHR BRC Translational Immunology Lab, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK; MRC Unit Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Viktor I KorolchukInstitute of Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Michael J LenardoLaboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; NIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD 20892, USA.
Sophie HambletonInstitute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK. Electronic address: sophie.hambleton@newcastle.ac.uk.
Helen C SuLaboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; NIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: hsu@niaid.nih.gov.
National Institutes of Health · USNewcastle University · GBNewcastle upon Tyne Hospitals NHS Foundation Trust · GBJohn Radcliffe Hospital · GBHeartlands Hospital · GBStarship Children's Health · NZUniversity of Birmingham · GBUniversity of British Columbia · CA

Funding

Defining New Human Immunodeficiency and Immunodysregulation DisordersZIAAI001059 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SU, HELEN CHUN-HUI · 2009 to 2025
$20.5M
Molecular Pathways of Programmed Cell Death And Viral CytopathicityZIAAI000718 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SU, HELEN · 2009 to 2024
$4.5M
Biotechnology and Biological Sciences Research Council BB/G021422/1CIHR MOP-133691Intramural NIH HHS ZIA AI001059Medical Research CouncilWellcome Trust 103830
6 · The paper itself

Abstract

Proteasomes and lysosomes constitute the major cellular systems that catabolize proteins to recycle free amino acids for energy and new protein synthesis. Tripeptidyl peptidase II (TPPII) is a large cytosolic proteolytic complex that functions in tandem with the proteasome-ubiquitin protein degradation pathway. We found that autosomal recessive TPP2 mutations cause recurrent infections, autoimmunity, and neurodevelopmental delay in humans. We show that a major function of TPPII in mammalian cells is to maintain amino acid levels and that TPPII-deficient cells compensate by increasing lysosome number and proteolytic activity. However, the overabundant lysosomes derange cellular metabolism by consuming the key glycolytic enzyme hexokinase-2 through chaperone-mediated autophagy. This reduces glycolysis and impairs the production of effector cytokines, including IFN-γ and IL-1β. Thus, TPPII controls the balance between intracellular amino acid availability, lysosome number, and glycolysis, which is vital for adaptive and innate immunity and neurodevelopmental health.

Indexed as

Adaptive ImmunityGlycolysisImmunity, InnateProteolysisAmino Acid SequenceAminopeptidasesAnimalsDipeptidyl-Peptidases and Tripeptidyl-PeptidasesFemaleHumansImmunologic Deficiency SyndromesLysosomesMaleModels, MolecularMolecular Sequence DataPedigreeAminopeptidasesDipeptidyl-Peptidases and Tripeptidyl-PeptidasesSerine Endopeptidasestripeptidyl-peptidase 2

Identifiers

PMID25525876
PMCPMC4297473
OpenAlexW2010181602

What OpenQuestion holds

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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.