Evidence map›Paper›PMID 29685892›Full record

ArticleJournal of cell science2018

Expansion of DUB functionality generated by alternative isoforms - USP35, a case study.

Pawel Leznicki, Jayaprakash Natarajan, Gerd Bader, Walter Spevak, Andreas Schlattl, Syed Arif Abdul Rehman, Deepika Pathak, Simone Weidlich, Andreas Zoephel, Marie C Bordone and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of cell science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
0.9field-weighted citation impact, top 26% 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, 30 citations in OpenAlex.

  1. Review
  2. Research progress of DUB enzyme in breast cancer.Clinical and experimental medicine · 2025
    Review
  3. Article
  4. AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025
    Review
  5. Review
  6. Article
  7. Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis.International journal of molecular sciences · 2021
    Article
  18. A Nucleolar Isoform of theFrontiers in cell and developmental biology · 2020
    Article
  19. Review
  20. Review
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

13 authors at 3 institutions in 3 countries.

Pawel LeznickiMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK pawel.leznicki@manchester.ac.uk ykulathu@dundee.ac.uk.ORCID 0000-0002-2687-107X
Jayaprakash NatarajanMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Gerd BaderBoehringer Ingelheim RCV GmbH & Co KG, Dr. Boehringer Gasse 5-11, 1120 Vienna, Austria.
Walter SpevakBoehringer Ingelheim RCV GmbH & Co KG, Dr. Boehringer Gasse 5-11, 1120 Vienna, Austria.ORCID 0000-0002-1738-7657
Andreas SchlattlBoehringer Ingelheim RCV GmbH & Co KG, Dr. Boehringer Gasse 5-11, 1120 Vienna, Austria.
Syed Arif Abdul RehmanMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Deepika PathakMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Simone WeidlichMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Andreas ZoephelBoehringer Ingelheim RCV GmbH & Co KG, Dr. Boehringer Gasse 5-11, 1120 Vienna, Austria.
Marie C BordoneInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.
Nuno L Barbosa-MoraisInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.
Guido BoehmeltBoehringer Ingelheim RCV GmbH & Co KG, Dr. Boehringer Gasse 5-11, 1120 Vienna, Austria.
Yogesh KulathuMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK pawel.leznicki@manchester.ac.uk ykulathu@dundee.ac.uk.ORCID 0000-0002-3274-1642
University of Dundee · GBBoehringer Ingelheim (Austria) · ATUniversity of Lisbon · PT

Funding

Medical Research Council MC_UU_12016/6
6 · The paper itself

Abstract

Protein ubiquitylation is a dynamic post-translational modification that can be reversed by deubiquitylating enzymes (DUBs). It is unclear how the small number (∼100) of DUBs present in mammalian cells regulate the thousands of different ubiquitylation events. Here, we analysed annotated transcripts of human DUBs and found ∼300 ribosome-associated transcripts annotated as protein coding, which thus increases the total number of DUBs. By using USP35, a poorly studied DUB, as a case study, we provide evidence that alternative isoforms contribute to the functional expansion of DUBs. We show that there are two different USP35 isoforms that localise to different intracellular compartments and have distinct functions. Our results reveal that isoform 1 is an anti-apoptotic factor that inhibits staurosporine- and TNF-related apoptosis-inducing ligand (TRAIL; also known as TNFSF10)-induced apoptosis. In contrast, USP35 isoform 2 is an integral membrane protein of the endoplasmic reticulum (ER) that is also present at lipid droplets. Manipulations of isoform 2 levels cause rapid ER stress, likely through deregulation of lipid homeostasis, and lead to cell death. Our work highlights how alternative isoforms provide functional expansion of DUBs and sets directions for future research.This article has an associated First Person interview with the first author of the paper.

Indexed as

ApoptosisEndopeptidasesEndoplasmic ReticulumHeLa CellsHumansProtein IsoformsProtein TransportUbiquitinUbiquitinationUbiquitin ThiolesteraseEndopeptidasesProtein IsoformsUbiquitinUbiquitin ThiolesteraseUSP35 protein, humanApoptosisDeubiquitinaseEndoplasmic reticulumLipid dropletsUbiquitin signalling

Identifiers

PMID29685892
PMCPMC6031330
OpenAlexW2802892343

What OpenQuestion holds

Textmetadata
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.