Evidence map›Paper›PMID 27377765›Full record

ArticleImmunology and cell biology2016

Mevalonate kinase deficiency leads to decreased prenylation of Rab GTPases.

Julie Jurczyluk, Marcia A Munoz, Oliver P Skinner, Ryan C Chai, Naveid Ali, Umaimainthan Palendira, Julian Mw Quinn, Alexandra Preston, Stuart G Tangye, Andrew J Brown and 4 more

Open access · hybridAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunology and cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Case Report: Clinical application of anFrontiers in pediatrics · 2025
    Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. [Clinical symptoms of autoinflammatory diseases].Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete · 2020
    Review
  16. Article
  17. Article
  18. Inborn errors of metabolism.Handbook of clinical neurology · 2019
    Review
  19. Review
  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

14 authors at 5 institutions in 1 country.

Julie JurczylukGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Australia, Sydney, New South Wales, Australia.
Marcia A MunozGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Australia, Sydney, New South Wales, Australia.
Oliver P SkinnerGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Australia, Sydney, New South Wales, Australia.
Ryan C ChaiGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Australia, Sydney, New South Wales, Australia.
Naveid AliGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Australia, Sydney, New South Wales, Australia.
Umaimainthan PalendiraGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Australia, Sydney, New South Wales, Australia.
Julian Mw QuinnGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Australia, Sydney, New South Wales, Australia.
Alexandra PrestonGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Australia, Sydney, New South Wales, Australia.
Stuart G TangyeGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Australia, Sydney, New South Wales, Australia.
Andrew J BrownSchool of Biotechnology & Biomolecular Sciences, UNSW Australia, Sydney, New South Wales, Australia.
Elizabeth ArgentDepartment of General Paediatrics, Sydney Children's Hospital, Randwick, New South Wales, Australia.
John B ZieglerSchool of Women's and Children's Health, UNSW Australia, Sydney, New South Wales, Australia.
Sam MehrDepartment of Immunology and Allergy, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
Michael J RogersGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Australia, Sydney, New South Wales, Australia.
Garvan Institute of Medical Research · AUSt Vincent's Clinic · AUSydney Children's Hospital · AUChildren's Hospital at Westmead · AUUNSW Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mevalonate kinase deficiency (MKD) is caused by mutations in a key enzyme of the mevalonate-cholesterol biosynthesis pathway, leading to recurrent autoinflammatory disease characterised by enhanced release of interleukin-1β (IL-1β). It is currently believed that the inflammatory phenotype of MKD is triggered by temperature-sensitive loss of mevalonate kinase activity and reduced biosynthesis of isoprenoid lipids required for the prenylation of small GTPase proteins. However, previous studies have not clearly shown any change in protein prenylation in patient cells under normal conditions. With lymphoblast cell lines from two compound heterozygous MKD patients, we used a highly sensitive in vitro prenylation assay, together with quantitative mass spectrometry, to reveal a subtle accumulation of unprenylated Rab GTPases in cells cultured for 3 days or more at 40 °C compared with 37 °C. This included a 200% increase in unprenylated Rab7A, Rab14 and Rab1A. Inhibition of sterol regulatory element-binding protein (SREBP) activation by fatostatin led to more pronounced accumulation of unprenylated Rab proteins in MKD cells but not parent cells, suggesting that cultured MKD cells may partially overcome the loss of isoprenoid lipids by SREBP-mediated upregulation of enzymes required for isoprenoid biosynthesis. Furthermore, while inhibition of Rho/Rac/Rap prenylation promoted the release of IL-1β, specific inhibition of Rab prenylation by NE10790 had no effect in human peripheral blood mononuclear cells or human THP-1 monocytic cells. These studies demonstrate for the first time that mutations in mevalonate kinase can lead to a mild, temperature-induced defect in the prenylation of small GTPases, but that loss of prenylated Rab GTPases is not the cause of enhanced IL-1β release in MKD.

Indexed as

Protein PrenylationCell LineChildChild, PreschoolFemaleHumansInterleukin-1betaIsotope LabelingLeukocytes, MononuclearMaleMevalonate Kinase DeficiencyPyridinesrab GTP-Binding ProteinsSterol Regulatory Element Binding Protein 1TemperatureThiazolesfatostatinInterleukin-1betaPyridinesrab GTP-Binding ProteinsSterol Regulatory Element Binding Protein 1Thiazoles

Identifiers

PMID27377765
PMCPMC5122740
OpenAlexW2462156962

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.