Evidence map›Paper›PMID 35210618›Full record

ArticleNature chemical biology2022

Deubiquitinase-targeting chimeras for targeted protein stabilization.

Nathaniel J Henning, Lydia Boike, Jessica N Spradlin, Carl C Ward, Gang Liu, Erika Zhang, Bridget P Belcher, Scott M Brittain, Matthew J Hesse, Dustin Dovala and 14 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
183citing papers in PubMed, 1 pooled it
24.2field-weighted citation impact, top 1% 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

183 citing papers in PubMed, 1 synthesis or guideline pooled it, 300 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Selective Modulation of OTUB1 Noncanonical Function via a bioPhosTAC Strategy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  12. Proteomics-Driven Strategies for Proximity-Inducing Drug Discovery.Angewandte Chemie (International ed. in English) · 2026
    Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Covalent Reprogramming of Kinase Binders to Modulate Protein Abundance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 2 institutions in 1 country.

Nathaniel J Henning *Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA.
Lydia Boike *Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA.
Jessica N SpradlinDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-7278-6645
Carl C WardNovartis-Berkeley Center for Proteomics and Chemistry Technologies, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-1188-4839
Gang LiuNovartis-Berkeley Center for Proteomics and Chemistry Technologies, Berkeley, CA, USA.
Erika ZhangDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA.
Bridget P BelcherDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-4837-9390
Scott M BrittainNovartis-Berkeley Center for Proteomics and Chemistry Technologies, Berkeley, CA, USA.
Matthew J HesseNovartis-Berkeley Center for Proteomics and Chemistry Technologies, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-4759-5086
Dustin DovalaNovartis-Berkeley Center for Proteomics and Chemistry Technologies, Berkeley, CA, USA.
Lynn M McGregorNovartis-Berkeley Center for Proteomics and Chemistry Technologies, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-4310-2384
Rachel Valdez MisiolekNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
Lindsey W PlasschaertNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
David J RowlandsNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
Feng WangNovartis-Berkeley Center for Proteomics and Chemistry Technologies, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-4322-2127
Andreas O FrankNovartis-Berkeley Center for Proteomics and Chemistry Technologies, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-2330-3974
Daniel FullerNovartis-Berkeley Center for Proteomics and Chemistry Technologies, Berkeley, CA, USA.
Abigail R EstesDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA.
Katelyn L RandalDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA.
Anoohya PanidapuDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA.
Jeffrey M McKennaNovartis-Berkeley Center for Proteomics and Chemistry Technologies, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-2978-5652
John A TallaricoNovartis-Berkeley Center for Proteomics and Chemistry Technologies, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-8040-8422
Markus SchirleNovartis-Berkeley Center for Proteomics and Chemistry Technologies, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-4933-2623
Daniel K NomuraDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA. dnomura@berkeley.edu.ORCID http://orcid.org/0000-0003-1614-8360
Novartis (United States) · USInnovative Genomics Institute · US

Funding

Harnessing E3 Ligases for Cancer TherapyR01CA240981 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI Daniel Nomura · 2019 to 2026
$4.3M
Acquisition of a Cryoprobe and Related Accessories for a 600 MHz NMR Spectrometer to Support Health Research Activities at the University of California, BerkeleyS10OD024998 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI HARTWIG, JOHN F · 2018 to 2018
$265k
Targeted Protein Stabilization PlatformsF31CA268278 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI HENNING, NATHANIEL JAMES · 2022 to 2022
$25k
NCI NIH HHS F31 CA268278NCI NIH HHS R01 CA240981NIH HHS S10 OD024998
6 · The paper itself

Abstract

Many diseases are driven by proteins that are aberrantly ubiquitinated and degraded. These diseases would be therapeutically benefited by targeted protein stabilization (TPS). Here we present deubiquitinase-targeting chimeras (DUBTACs), heterobifunctional small molecules consisting of a deubiquitinase recruiter linked to a protein-targeting ligand, to stabilize the levels of specific proteins degraded in a ubiquitin-dependent manner. Using chemoproteomic approaches, we discovered the covalent ligand EN523 that targets a non-catalytic allosteric cysteine C23 in the K48-ubiquitin-specific deubiquitinase OTUB1. We showed that a DUBTAC consisting of our EN523 OTUB1 recruiter linked to lumacaftor, a drug used to treat cystic fibrosis that binds ΔF508-cystic fibrosis transmembrane conductance regulator (CFTR), robustly stabilized ΔF508-CFTR protein levels, leading to improved chloride channel conductance in human cystic fibrosis bronchial epithelial cells. We also demonstrated stabilization of the tumor suppressor kinase WEE1 in hepatoma cells. Our study showcases covalent chemoproteomic approaches to develop new induced proximity-based therapeutic modalities and introduces the DUBTAC platform for TPS.

Indexed as

Cystic FibrosisChimeraCystic Fibrosis Transmembrane Conductance RegulatorDeubiquitinating EnzymesHumansLigandsUbiquitinCystic Fibrosis Transmembrane Conductance RegulatorDeubiquitinating EnzymesLigandsUbiquitin

Identifiers

PMID35210618
PMCPMC10125259
OpenAlexW4225364558

What OpenQuestion holds

Textmetadata
LicenceTDM
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.