Evidence map›Paper›PMID 40841494›Full record

ArticleNature chemical biology2026

Highly specific intracellular ubiquitination of a small molecule.

Weicheng Li, Enrique M Garcia-Rivera, Dylan C Mitchell, Joel M Chick, Micah Maetani, Rohit Bhadoria, John M Knapp, Ryosuke Misu, Geoffrey M Matthews, Ryosuke Shirasaki and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Weicheng Li *Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-6356-2674
Enrique M Garcia-Rivera *Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1203-2918
Dylan C MitchellDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Joel M ChickDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Micah MaetaniBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0905-799X
Rohit BhadoriaDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
John M KnappBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Ryosuke MisuDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0009-0004-2019-353X
Geoffrey M MatthewsDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Ryosuke ShirasakiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0009-0000-5629-1394
Ricardo de Matos SimoesDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1700-5276
Vasanthi ViswanathanBroad Institute of MIT and Harvard, Cambridge, MA, USA.
John L PuliceDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2561-9358
Matthew G ReesBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2987-7581
Jennifer A RothBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-5117-5586
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7626-0034
Constantine S MitsiadesDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2321-8005
Cigall KadochDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Stuart L SchreiberBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-1922-7558
Jonathan M L OstremDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA. jonathan.ostrem@ucsf.edu.ORCID http://orcid.org/0000-0001-9085-1615

Funding

Physician Scientist Training in Cancer ResearchT32CA009172 · NCI · DANA-FARBER CANCER INSTITUTE · PI Jennifer R Brown, James A. DeCaprio · 1985 to 2026
$17.1M
Targeting vulnerabilities of therapy-resistant cancer cell states with small moleculesU01CA217848 · NCI · BROAD INSTITUTE, INC. · PI SCHREIBER, STUART L · 2017 to 2021
$5.8M
Translating novel cancer targets and mechanisms from the CTD^2 Network using molecular gluesU01CA272612 · NCI · BROAD INSTITUTE, INC. · PI CLEMONS, PAUL ANDREW, SCHREIBER, STUART L · 2022 to 2023
$1.9M
NCI NIH HHS T32 CA009172U.S. Department of Health & Human Services | NIH | Center for Scientific Review (NIH Center for Scientific Review) 1DP2CA195762U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 3P30CA082103-22S1U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U01CA217848U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U01CA272612U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) GM097645
6 · The paper itself

Abstract

Ubiquitin is a small, highly conserved protein that acts as a posttranslational modification in eukaryotes. Ubiquitination of proteins frequently serves as a degradation signal, marking them for disposal by the proteasome. Here we report a novel small molecule from a diversity-oriented synthesis library, BRD1732, that is directly ubiquitinated in cells, resulting in dramatic accumulation of inactive ubiquitin monomers and polyubiquitin chains, which causes broad inhibition of the ubiquitin-proteasome system. Ubiquitination of BRD1732 and its associated cytotoxicity are stereospecific and dependent on two homologous E3 ubiquitin ligases, RNF19A and RNF19B, and their shared E2 conjugating enzyme, UBE2L3. Our finding opens the possibility for indirect ubiquitination of a target through a ubiquitinated bifunctional small molecule and more broadly raises the potential for posttranslational modification in trans.

Indexed as

Small Molecule LibrariesUbiquitinUbiquitinationHumansProteasome Endopeptidase ComplexUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesProteasome Endopeptidase ComplexSmall Molecule LibrariesUbiquitinUbiquitin-Conjugating EnzymesUbiquitin-Protein Ligases

Identifiers

PMID40841494
PMCPMC13038411

What OpenQuestion holds

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LicenceCC BY
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.