Evidence map›Paper›PMID 42239404›Full record

ArticlebioRxiv : the preprint server for biology2026

Ratiometric transcriptional activation by protein degradation.

Melissa A Gray, Katelyn L Randal, Jennifer A Co, Michelle T Tang, Athena Z Xue, Sophia W Chen, Hlib Razumkov, Qusay Q Omran, David E Solow-Cordero, Jeonghye Yu and 5 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. 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.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Melissa A GrayDepartment of Chemistry, Stanford University, Stanford, CA, 94305, USA.
Katelyn L RandalDepartment of Chemistry, Stanford University, Stanford, CA, 94305, USA.
Jennifer A CoDepartment of Chemistry, Stanford University, Stanford, CA, 94305, USA.
Michelle T TangDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA.
Athena Z XueDepartment of Chemistry, Stanford University, Stanford, CA, 94305, USA.
Sophia W ChenDepartment of Chemistry, Stanford University, Stanford, CA, 94305, USA.
Hlib RazumkovDepartment of Chemistry, Stanford University, Stanford, CA, 94305, USA.
Qusay Q OmranDepartment of Genetics, Stanford University, Stanford, CA 94305, USA.
David E Solow-CorderoHigh-Throughput Screening Knowledge Center, Sarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.
Jeonghye YuDepartment of Chemistry, Stanford University, Stanford, CA, 94305, USA.
Stephanie A RobinsonDepartment of Chemistry, Stanford University, Stanford, CA, 94305, USA.
Cara A StarnbachDepartment of Chemistry, Stanford University, Stanford, CA, 94305, USA.
Nathanael S GrayDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA.
Steven M CorselloDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA.
Steven M BanikDepartment of Chemistry, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0002-0544-6488

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8M
30-parameter FACSymphony A3 flow cytometer for Shared Resource LabS10OD026831 · OD · STANFORD UNIVERSITY · PI NOLAN, GARRY P · 2019 to 2019
$510k
NIGMS NIH HHS T32 GM007365NIH HHS S10 OD026831
6 · The paper itself

Abstract

Cells can respond to alterations in the abundances of specific proteins through transcriptional outputs. Synthetic approaches inspired by native post-transcriptional circuits that convert protein abundance changes into programmable gene expression would be transformative. Here, we discover and describe design principles that effectively convert protein degradation into transcriptional outputs in live cells. We define ratiometric transcriptional activation, where control over the ratio between a transcriptional inhibitor-protein of interest fusion and transcription factor enables detection of abundance changes with high sensitivity at scale. We show that ratiometric transcriptional activation can be implemented in single cells using triply orthogonal circuits or in multicellular pools, operating independently of mechanism of protein downregulation and enabling simultaneous detection of multiple protein downregulation events through outputs such as cell survival, fluorescent protein expression, or barcode sequencing. These circuits can be applied to oncogenic targets and enable discovery of new molecular glue degraders.

Identifiers

PMID42239404
PMCPMC13228303

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.