Evidence map›Paper›PMID 26731412›Full record

ArticlePloS one2016

Reversible Cysteine Acylation Regulates the Activity of Human Palmitoyl-Protein Thioesterase 1 (PPT1).

Michal Segal-Salto, Tamar Sapir, Orly Reiner

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

18 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. GABATranslational psychiatry · 2024
    Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Protein Lipidation by Palmitoylation and Myristoylation in Cancer.Frontiers in cell and developmental biology · 2021
    Review
  10. Review
  11. Complex StructuralG3 (Bethesda, Md.) · 2019
    Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. 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

3 authors at 1 institution in 1 country.

Michal Segal-SaltoThe Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel.
Tamar SapirThe Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel.
Orly ReinerThe Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel.
Weizmann Institute of Science · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mutations in the depalmitoylating enzyme gene, PPT1, cause the infantile form of Neuronal Ceroid Lipofuscinosis (NCL), an early onset neurodegenerative disease. During recent years there have been different therapeutic attempts including enzyme replacement. Here we show that PPT1 is palmitoylated in vivo and is a substrate for two palmitoylating enzymes, DHHC3 and DHHC7. The palmitoylated protein is detected in both cell lysates and medium. The presence of PPT1 with palmitoylated signal peptide in the cell medium suggests that a subset of the protein is secreted by a nonconventional mechanism. Using a mutant form of PPT1, C6S, which was not palmitoylated, we further demonstrate that palmitoylation does not affect intracellular localization but rather that the unpalmitoylated form enhanced the depalmitoylation activity of the protein. The calculated Vmax of the enzyme was significantly affected by the palmitoylation, suggesting that the addition of a palmitate group is reminiscent of adding a noncompetitive inhibitor. Thus, we reveal the existence of a positive feedback loop, where palmitoylation of PPT1 results in decreased activity and subsequent elevation in the amount of palmitoylated proteins. This positive feedback loop is likely to initiate a vicious cycle, which will enhance disease progression. The understanding of this process may facilitate enzyme replacement strategies.

Indexed as

AcylationCysteineHumansMutationNeuronal Ceroid-LipofuscinosesNeuronsThiolester HydrolasesCysteinepalmitoyl-protein thioesteraseThiolester Hydrolases

Identifiers

PMID26731412
PMCPMC4701722
OpenAlexW2225387417

What OpenQuestion holds

Textmetadata
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.