Evidence map›Paper›PMID 36289220›Full record

ArticleNature communications2022

Revealing β-TrCP activity dynamics in live cells with a genetically encoded biosensor.

Debasish Paul, Stephen C Kales, James A Cornwell, Marwa M Afifi, Ganesha Rai, Alexey Zakharov, Anton Simeonov, Steven D Cappell

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
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

9 citing papers in PubMed, 16 citations in OpenAlex.

  1. Distinct Stress Regulators in the CRL Family: Emerging Roles of F-Box Proteins: Cullin-RING Ligases and Stress-Sensing.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. CRL4Life science alliance · 2024
    Article
  8. Article
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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

8 authors at 2 institutions in 1 country.

Debasish PaulLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.ORCID 0000-0002-3909-4476
Stephen C KalesNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
James A CornwellLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.
Marwa M AfifiLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.ORCID 0000-0002-4877-7447
Ganesha RaiNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Alexey ZakharovNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Anton SimeonovNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Steven D CappellLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA. steven.cappell@nih.gov.ORCID 0000-0002-2885-7327
National Cancer Institute · USNational Institutes of Health · US

Funding

Control of cell cycle commitment by APCC-Cdh1ZIABC011830 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI CAPPELL, STEVEN · 2018 to 2025
$4.7M
Screening for small molecule modulators of SCFbTrCP ubiquitin ligase complexZIATR000455 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI RAI BANTUKALLU, GANESHA · 2022 to 2024
$600k
Intramural NIH HHS ZIA BC011830Intramural NIH HHS ZIA TR000455
6 · The paper itself

Abstract

The F-box protein beta-transducin repeat containing protein (β-TrCP) acts as a substrate adapter for the SCF E3 ubiquitin ligase complex, plays a crucial role in cell physiology, and is often deregulated in many types of cancers. Here, we develop a fluorescent biosensor to quantitatively measure β-TrCP activity in live, single cells in real-time. We find β-TrCP remains constitutively active throughout the cell cycle and functions to maintain discreet steady-state levels of its substrates. We find no correlation between expression levels of β-TrCP and β-TrCP activity, indicating post-transcriptional regulation. A high throughput screen of small-molecules using our reporter identifies receptor-tyrosine kinase signaling as a key axis for regulating β-TrCP activity by inhibiting binding between β-TrCP and the core SCF complex. Our study introduces a method to monitor β-TrCP activity in live cells and identifies a key signaling network that regulates β-TrCP activity throughout the cell cycle.

Indexed as

Biosensing TechniquesF-Box Proteinsbeta-Transducin Repeat-Containing ProteinsProtein-Tyrosine KinasesUbiquitin-Protein Ligasesbeta-Transducin Repeat-Containing ProteinsF-Box ProteinsProtein-Tyrosine KinasesUbiquitin-Protein Ligases

Identifiers

PMID36289220
PMCPMC9606124
OpenAlexW4307657347

What OpenQuestion holds

Textmetadata
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.