Evidence map›Paper›PMID 14673145›Full record

ArticleMolecular and cellular biology2004

Specific and covalent targeting of conjugating and deconjugating enzymes of ubiquitin-like proteins.

Joris Hemelaar, Anna Borodovsky, Benedikt M Kessler, David Reverter, Julie Cook, Nagamallesawari Kolli, Tudev Gan-Erdene, Keith D Wilkinson, Grace Gill, Christopher D Lima and 2 more

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

98 citing papers in PubMed, 206 citations in OpenAlex.

  1. Article
  2. Article
  3. Synthetic Strategies for Activity-Based Probes to Decode Ubiquitin-Like Modifiers.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026
    Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Chemical Tools for Probing the Ub/Ubl Conjugation Cascades.Chembiochem : a European journal of chemical biology · 2025
    Review
  10. Article
  11. Capturing the catalytic intermediates of parkin ubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  12. Article
  13. Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024
    Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Review

38 more citing papers are in PubMed but not listed here.

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

12 authors at 3 institutions in 1 country.

Joris HemelaarDepartment of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Anna Borodovsky
Benedikt M Kessler
David Reverter
Julie Cook
Nagamallesawari Kolli
Tudev Gan-Erdene
Keith D Wilkinson
Grace Gill
Christopher D Lima
Hidde L Ploegh
Huib Ovaa
Harvard University · USEmory University · USCornell University · US

Funding

Structural studies of ubiquitin-like protein modificationR01GM065872 · NIGMS · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI LIMA, CHRISTOPHER D. · 2002 to 2015
$4.9M
UBIQUITIN-DEPENDENT PROTEOLYSIS--SPECIFICITY/MECHANISMR01GM030308 · NIGMS · EMORY UNIVERSITY · PI WILKINSON, KEITH D · 1985 to 2010
$3.9M
Functions of Ub-like Proteins &Processing ProteasesR01GM066355 · NIGMS · EMORY UNIVERSITY · PI WILKINSON, KEITH D · 2002 to 2009
$2.5M
MECHANISMS AND FUNCTION OF PROTEIN DEGRADATIONF05TW005461 · FIC · EMORY UNIVERSITY · PI GAN ERDENE, TUDEVIIN · 2000 to 2001
$74k
FIC NIH HHS F05 TW005461FIC NIH HHS TW05461NIGMS NIH HHS GM30308NIGMS NIH HHS GM65872NIGMS NIH HHS GM66355NIGMS NIH HHS R01 GM030308NIGMS NIH HHS R01 GM065872NIGMS NIH HHS R01 GM066355
6 · The paper itself

Abstract

Modification of proteins by ubiquitin (Ub)-like proteins (UBLs) plays an important role in many cellular processes, including cell cycle progression, nuclear transport, and autophagy. Protein modification occurs via UBL-conjugating and -deconjugating enzymes, which presumably exert a regulatory function by determining the conjugation status of the substrate proteins. To target and identify UBL-modifying enzymes, we produced Nedd8, ISG15, and SUMO-1 in Escherichia coli and equipped them with a C-terminal electrophilic trap (vinyl sulfone [VS]) via an intein-based method. These C-terminally modified UBL probes reacted with purified UBL-activating (E1), -conjugating (E2), and -deconjugating enzymes in a covalent fashion. Modified UBLs were radioiodinated and incubated with cell lysates prepared from mouse cell lines and tissues to allow visualization of polypeptides reactive with individual UBL probes. The cell type- and tissue-specific labeling patterns observed for the UBL probes reflect distinct expression profiles of active enzymes, indicating tissue-specific functions of UBLs. We identify Ub C-terminal hydrolase L1 (UCH-L1) and DEN1/NEDP1/SENP8, in addition to UCH-L3, as proteases with specificity for Nedd8. The Ub-specific protease isopeptidase T/USP5 is shown to react with ISG15-VS. Furthermore, we demonstrate that the desumoylation enzyme SuPr-1 can be modified by SUMO-1-VS, a modification that is dependent on the SuPr-1 active-site cysteine. The UBL probes described here will be valuable tools for the further characterization of the enzymatic pathways that govern modification by UBLs.

Indexed as

AnimalsEndopeptidasesEnzymesMiceMolecular ProbesSulfonesSUMO-1 ProteinUbiquitinsdivinyl sulfoneEndopeptidasesEnzymesMolecular ProbesSulfonesSUMO-1 ProteinUbiquitins

Identifiers

PMID14673145
PMCPMC303361
OpenAlexW2121619038

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.