Evidence map›Paper›PMID 37461636›Full record

ArticlebioRxiv : the preprint server for biology2023

Bifunctional small molecules that induce nuclear localization and targeted transcriptional regulation.

William J Gibson, Ananthan Sadagopan, Veronika M Shoba, Amit Choudhary, Matthew Meyerson, Stuart L Schreiber

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

Article in bioRxiv : the preprint server for biology, 2023. 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, 11 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

William J GibsonBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Ananthan SadagopanBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Veronika M ShobaBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Amit ChoudharyBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Matthew MeyersonBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Stuart L SchreiberBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Broad Institute · US

Funding

NKX2-1 Enhancer Amplification and Lineage Addiction in Lung AdenocarcinomaR35CA197568 · NCI · DANA-FARBER CANCER INST · PI Matthew L. Meyerson · 2015 to 2026
$12.4M
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 R35 CA197568NCI NIH HHS U01 CA217848
6 · The paper itself

Abstract

The aberrant localization of proteins in cells is a key factor in the development of various diseases, including cancer and neurodegenerative disease. To better understand and potentially manipulate protein localization for therapeutic purposes, we engineered bifunctional compounds that bind to proteins in separate cellular compartments. We show these compounds induce nuclear import of cytosolic cargoes, using nuclear-localized BRD4 as a "carrier" for co-import and nuclear trapping of cytosolic proteins. We use this system to calculate kinetic constants for passive diffusion across the nuclear pore and demonstrate single-cell heterogeneity in response to these bifunctional molecules, with cells requiring high carrier to cargo expression for complete import. We also observe incorporation of cargoes into BRD4-containing condensates. Proteins shown to be substrates for nuclear transport include oncogenic mutant nucleophosmin (NPM1c) and mutant PI3K catalytic subunit alpha (PIK3CA

Identifiers

PMID37461636
PMCPMC10350064
OpenAlexW4383532500

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.