Evidence map›Paper›PMID 38328167›Full record

ArticlebioRxiv : the preprint server for biology2024

Highly specific intracellular ubiquitination of a small molecule.

Weicheng Li, Enrique M Garcia-Rivera, Dylan C Mitchell, Joel M Chick, Micah Maetani, John M Knapp, Geoffrey M Matthews, Ryosuke Shirasaki, Ricardo de Matos Simoes, Vasanthi Viswanathan and 8 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 4 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 3 institutions in 1 country.

Weicheng LiDepartment of Medicine, University of California, San Francisco; San Francisco, CA 94158, USA.ORCID 0000-0001-6356-2674
Enrique M Garcia-RiveraDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School; Boston, MA 02215, USA.ORCID 0000-0003-1203-2918
Dylan C MitchellDepartment of Cell Biology, Harvard Medical School; Boston, MA 02115, USA.
Joel M ChickDepartment of Cell Biology, Harvard Medical School; Boston, MA 02115, USA.
Micah MaetaniBroad Institute of MIT and Harvard; Cambridge, MA 02215, USA.ORCID 0000-0002-0905-799X
John M KnappBroad Institute of MIT and Harvard; Cambridge, MA 02215, USA.ORCID 0000-0002-1680-6549
Geoffrey M MatthewsDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School; Boston, MA 02215, USA.ORCID 0000-0002-2804-2021
Ryosuke ShirasakiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School; Boston, MA 02215, USA.
Ricardo de Matos SimoesDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School; Boston, MA 02215, USA.ORCID 0000-0002-1700-5276
Vasanthi ViswanathanBroad Institute of MIT and Harvard; Cambridge, MA 02215, USA.ORCID 0000-0001-9878-3629
John L PuliceDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School; Boston, MA 02215, USA.ORCID 0000-0002-2561-9358
Matthew G ReesBroad Institute of MIT and Harvard; Cambridge, MA 02215, USA.
Jennifer A RothBroad Institute of MIT and Harvard; Cambridge, MA 02215, USA.ORCID 0000-0002-5117-5586
Steven P GygiDepartment of Cell Biology, Harvard Medical School; Boston, MA 02115, USA.ORCID 0000-0001-7626-0034
Constantine S MitsiadesDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School; Boston, MA 02215, USA.
Cigall KadochDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School; Boston, MA 02215, USA.ORCID 0000-0002-4058-5985
Stuart L SchreiberBroad Institute of MIT and Harvard; Cambridge, MA 02215, USA.ORCID 0000-0003-1922-7558
Jonathan M L OstremDepartment of Medicine, University of California, San Francisco; San Francisco, CA 94158, USA.ORCID 0000-0001-9085-1615
Broad Institute · USHarvard University · USUniversity of California, San Francisco · US

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer Leigh Clarke · 1999 to 2026
$209.7M
Targeting vulnerabilities of therapy-resistant cancer cell states with small moleculesU01CA217848 · NCI · BROAD INSTITUTE, INC. · PI SCHREIBER, STUART L · 2017 to 2021
$5.8M
Reversing Oncogenic BAF Complex Structure & Function: New Therapeutic ApproachesDP2CA195762 · NCI · DANA-FARBER CANCER INST · PI KADOCH, CIGALL · 2014 to 2014
$2.6M
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 DP2 CA195762NCI NIH HHS P30 CA082103NCI NIH HHS U01 CA217848NCI NIH HHS U01 CA272612
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 causing broad inhibition of the ubiquitin-proteasome system. Ubiquitination of BRD1732 and its associated cytotoxicity are stereospecific and dependent upon two homologous E3 ubiquitin ligases, RNF19A and RNF19B. 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

Identifiers

PMID38328167
PMCPMC10849632
OpenAlexW4391296308

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.