Evidence map›Paper›PMID 40902594›Full record

ArticleCell chemical biology2025

Pharmacologic interrogation of USP28 cellular function in p53 signaling.

Ariana S Bratt, Susan Kilgas, Maria I Tarazona Guzman, Robert S Magin, Isabella Jaen Maisonet, Cara A Starnbach, Wei Pin Teh, Anthony C Varca, Bin Hu, Esteban Tarazona Guzman and 7 more

Abstract read
In one paragraph

Article in Cell chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

17 authors.

Ariana S BrattDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Susan KilgasDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Maria I Tarazona GuzmanDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Robert S MaginDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Isabella Jaen MaisonetDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Cara A StarnbachDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Wei Pin TehDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Anthony C VarcaDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Bin HuDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Esteban Tarazona GuzmanDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Hyuk-Soo SeoDepartment of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Chemical Biology Program, Dana-Farber Cancer Institute, Boston, MA, USA.
Sirano Dhe-PaganonDepartment of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Chemical Biology Program, Dana-Farber Cancer Institute, Boston, MA, USA.
Nicholas M GirardiDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Guillaume AdelmantDepartment of Oncologic Pathology and Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA.
Jarrod A MartoDepartment of Oncologic Pathology and Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA.
Dipanjan ChowdhuryDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Sara J BuhrlageDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: saraj_buhrlage@dfci.harvard.edu.

Funding

User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI Frank V Murphy · 2018 to 2026
$34.2M
Enhanced radiotherapy for pediatric glioma via synthetic lethal vulnerabilitiesR01CA284565 · NCI · DANA-FARBER CANCER INST · PI Dipanjan Chowdhury, DAPHNE A. HAAS-KOGAN · 2024 to 2026
$4.2M
Novel Screening Platform for Discovery of DUB Targeting ProbesR01CA233800 · NCI · DANA-FARBER CANCER INST · PI BUHRLAGE, SARA J, MARTO, JARROD A. · 2019 to 2022
$2.5M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
Elucidating the molecular mechanism and physiological relevance of TIRR mediated inhibition of p53R01CA264900 · NCI · DANA-FARBER CANCER INST · PI Dipanjan Chowdhury · 2022 to 2026
$1.9M
Investigating 53BP1 'dephosphorylation' as a critical determinant of PARPR01CA208244 · NCI · DANA-FARBER CANCER INST · PI CHOWDHURY, DIPANJAN · 2017 to 2021
$1.9M
TIRR/53BP1 complex regulates mitotic fidelity and immune-mediated radiation responseR01CA301574 · NCI · DANA-FARBER CANCER INST · PI Dipanjan Chowdhury, Alexander Spektor · 2026 to 2026
$683k
Tools for DUB Drug DiscoveryR21CA247671 · NCI · DANA-FARBER CANCER INST · PI BUHRLAGE, SARA J, MARTO, JARROD A. · 2020 to 2021
$648k
NCI NIH HHS R01 CA208244NCI NIH HHS R01 CA233800NCI NIH HHS R01 CA264900NCI NIH HHS R01 CA284565NCI NIH HHS R01 CA301574NCI NIH HHS R21 CA247671NIGMS NIH HHS P30 GM124165NIH HHS S10 OD021527
6 · The paper itself

Abstract

Deubiquitinating enzymes (DUBs) are crucial regulators of ubiquitin signaling and protein degradation that remain incompletely understood in part due to the lack of high-quality chemical probes. To address this challenge, we developed CAS-010, a low nanomolar, ubiquitin-competitive inhibitor of USP28 that demonstrates preferential activity against USP28 over other DUBs, while also exhibiting some activity against the closely related USP25. We rationalized our SAR trends and observed selectivity using a crystal structure of USP28 in complex with an inhibitor. We validated on-target effects of CAS-010 on the negative regulation of p53 transactivation in the wild-type setting. We demonstrated that CAS-010 disrupts the 53BP1-USP28 interaction, and more broadly showed that USP28 catalytic activity contributes to this key interaction. Taken together, CAS-010 and the accompanying negative control compound WPT-086 and inhibitor-resistant mutant provide well-validated tools for further characterizing the role of USP28 in p53-mediated effect on cell cycle control and cell fate.

Indexed as

Signal TransductionTumor Suppressor Protein p53Ubiquitin ThiolesteraseHumansMolecular StructureStructure-Activity RelationshipTumor Suppressor Protein p53Ubiquitin ThiolesteraseUSP28 protein, human53BP1chemical probecrystal structuredeubiquitinating enzymeDUBp53p53 transcriptional regulationUSP28

Identifiers

PMID40902594
PMCPMC13078789

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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.