Evidence map›Paper›PMID 33007217›Full record

ArticleCell chemical biology2021

Proteomics-Based Identification of DUB Substrates Using Selective Inhibitors.

Jonathan W Bushman, Katherine A Donovan, Nathan J Schauer, Xiaoxi Liu, Wanyi Hu, Anthony C Varca, Sara J Buhrlage, Eric S Fischer

Abstract read
In one paragraph

Article in Cell chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
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

20 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Deubiquitinases in cancer.Nature reviews. Cancer · 2023
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  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

8 authors.

Jonathan W BushmanDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Katherine A DonovanDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Nathan J SchauerDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Xiaoxi LiuDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Wanyi HuDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Anthony C VarcaDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Sara J BuhrlageDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Eric S FischerDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: eric_fischer@dfci.harvard.edu.

Funding

Degrading therapeutically important kinases using small moleculesR01CA218278 · NCI · STANFORD UNIVERSITY · PI Eric Sebastian Fischer, NATHANAEL Schiander GRAY · 2019 to 2026
$4.6M
The molecular basis of IMiD induced neo-substrate recruitment to the CRL4CRBN ubiquitin E3 ligase.R01CA214608 · NCI · DANA-FARBER CANCER INST · PI Eric Sebastian Fischer · 2017 to 2026
$4.0M
NCI NIH HHS R01 CA214608NCI NIH HHS R01 CA218278
6 · The paper itself

Abstract

Deubiquitinating enzymes (DUBs) catalyze the removal of ubiquitin, thereby reversing the activity of E3 ubiquitin ligases and are central to the control of protein abundance and function. Despite the growing interest in DUBs as therapeutic targets, cellular functions for DUBs remain largely unknown and technical challenges often preclude the identification of DUB substrates in a comprehensive manner. Here, we demonstrate that treatment with potent DUB inhibitors coupled to mass spectrometry-based proteomics can identify DUB substrates at a proteome-wide scale. We applied this approach to USP7, a DUB widely investigated as a therapeutic target and identified many known substrates and additional targets. We demonstrate that USP7 substrates are enriched for DNA repair enzymes and E3 ubiquitin ligases. This work provides not only a comprehensive annotation of USP7 substrates, but a general protocol widely applicable to other DUBs, which is critical for translational development of DUB targeted agents.

Indexed as

ProteomicsBiocatalysisCells, CulturedEnzyme InhibitorsHumansSubstrate SpecificityUbiquitinationUbiquitin-Specific Peptidase 7Enzyme InhibitorsUbiquitin-Specific Peptidase 7USP7 protein, humanchemical probedeubiquitinating enzymesdrug discoveryDUBsproteomics

Identifiers

PMID33007217
PMCPMC7855594

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Registered trials

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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.