Evidence map›Paper›PMID 38597345›Full record

ArticleJournal of the American Chemical Society2024

USP7-Based Deubiquitinase-Targeting Chimeras Stabilize AMPK.

Jing Liu, Xiaoping Hu, Kaixiu Luo, Yan Xiong, Li Chen, Zhen Wang, Hiroyuki Inuzuka, Chao Qian, Xufen Yu, Ling Xie and 6 more

Abstract read
In one paragraph

Article in Journal of the American Chemical Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing 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

25 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Covalent Reprogramming of Kinase Binders to Modulate Protein Abundance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Emerging biologic modalities for targeted protein degradation.The Journal of biological chemistry · 2026
    Review
  12. Review
  13. Review
  14. OTU deubiquitinases in disease: roles and targeting.Trends in molecular medicine · 2026
    Review
  15. Covalent Reprogramming of Kinase Binders to Modulate Protein Homeostasis.bioRxiv : the preprint server for biology · 2025
    Article
  16. [Potential of early diagnosis and targeted therapy for Klotho protein in chronic kidney disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025
    Review
  17. Small-molecule allosteric activator of ubiquitin-specific protease 7 (USP7).Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Targeting G9a-miScience · 2025
    Article
  19. Article
  20. Harnessing the Deubiquitinase USP1 for Targeted Protein Stabilization.Journal of the American Chemical Society · 2025
    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

16 authors.

Jing LiuDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, United States.
Xiaoping HuMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Kaixiu LuoMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Yan XiongMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Li ChenDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, United States.
Zhen WangDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, United States.
Hiroyuki InuzukaDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, United States.
Chao QianMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Xufen YuMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.ORCID 0000-0001-7794-7890
Ling XieDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Adil MuneerDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.ORCID 0000-0002-8605-3351
Dingpeng ZhangDepartment of Cancer Biology, Dana-Farber Cancer Institute; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02215, United States.
Joao A PauloDepartment of Cell Biology, Blavatnik Institute at Harvard Medical School, Boston, Massachusetts 02115, United States.
Xian ChenDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Jian JinMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.ORCID 0000-0002-2387-3862
Wenyi WeiDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, United States.ORCID 0000-0003-0512-3811

Funding

THE TISCH CANCER INSTITUTE - CANCER CENTER SUPPORT GRANTP30CA196521 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Ramon E Parsons · 2015 to 2026
$35.4M
Deciphering the physiological role and interplay between ubiquitination and phosphorylation pathways to guide targeted cancer therapiesR35CA253027 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Wenyi Wei · 2020 to 2026
$6.2M
Advancing Multiplexed Isobaric Tag-based Strategies for Proteome ProfilingR01GM132129 · NIGMS · HARVARD MEDICAL SCHOOL · PI PAULO, JOAO A · 2019 to 2023
$1.7M
Molecular mechanisms of CIB1 signalingR01GM133107 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CHEN, XIAN · 2019 to 2020
$617k
An AVANCE NEO 400 MHz NMR Spectrometer for Chemical Biology and Drug DiscoveryS10OD028504 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ZHOU, MING-MING · 2020 to 2020
$599k
An AVANCE NEO 600 MHz NMR Spectrometer System for Structural and Chemical BiologyS10OD025132 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ZHOU, MING-MING · 2019 to 2019
$535k
Deciphering the non-canonical function of the histone methyltransferase G9a in the etiology of ADR21AG071229 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CHEN, XIAN · 2021 to 2022
$428k
Novel therapeutic intervention of early-stage T1DR41DK133051 · NIDDK · TRANSCHROMIX, LLC. · PI CHEN, XIAN · 2023 to 2023
$301k
NCI NIH HHS P30 CA196521NCI NIH HHS R35 CA253027NIA NIH HHS R21 AG071229NIDDK NIH HHS R41 DK133051NIGMS NIH HHS R01 GM132129NIGMS NIH HHS R01 GM133107NIH HHS S10 OD025132NIH HHS S10 OD028504
6 · The paper itself

Abstract

Deubiquitinase-targeting chimeras (DUBTACs) have been recently developed to stabilize proteins of interest, which is in contrast to targeted protein degradation (TPD) approaches that degrade disease-causing proteins. However, to date, only the OTUB1 deubiquitinase has been utilized to develop DUBTACs via an OTUB1 covalent ligand, which could unexpectedly compromise the endogenous function of OTUB1 owing to its covalent nature. Here, we show for the first time that deubiquitinase USP7 can be harnessed for DUBTAC development. Based on a noncovalent ligand of USP7, we developed USP7-based DUBTACs that stabilized the ΔF508-CFTR mutant protein as effectively as the previously reported OTUB1-based DUBTAC. Importantly, using two different noncovalent ligands of USP7, we developed the first AMPK DUBTACs that appear to selectively stabilize different isoforms of AMPKβ, leading to elevated AMPK signaling. Overall, these results highlight that, in addition to OTUB1, USP7 can be leveraged to develop DUBTACs, thus significantly expanding the limited toolbox for targeted protein stabilization and the development of novel AMPK DUBTACs as potential therapeutics.

Identifiers

PMID38597345
PMCPMC12107614

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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.