Evidence map›Paper›PMID 38965383›Full record

ArticleNature chemical biology2024

A CRISPR activation screen identifies FBXO22 supporting targeted protein degradation.

Ananya A Basu, Chenlu Zhang, Isabella A Riha, Assa Magassa, Miguel A Campos, Alana G Caldwell, Felicia Ko, Xiaoyu Zhang

Abstract read
In one paragraph

Article in Nature chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing 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

34 citing papers in PubMed.

  1. Article
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  5. Article
  6. Article
  7. Covalent Reprogramming of Kinase Binders to Modulate Protein Abundance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  8. Article
  9. Article
  10. Review
  11. Small-molecule degraders for oncogenic KRASNature communications · 2026
    Article
  12. Article
  13. Review
  14. Review
  15. Covalent Reprogramming of Kinase Binders to Modulate Protein Homeostasis.bioRxiv : the preprint server for biology · 2025
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Ananya A BasuDepartment of Chemistry, Northwestern University, Evanston, IL, USA.ORCID http://orcid.org/0000-0002-1427-5326
Chenlu ZhangDepartment of Chemistry, Northwestern University, Evanston, IL, USA.ORCID http://orcid.org/0000-0003-4171-5099
Isabella A RihaDepartment of Chemistry, Northwestern University, Evanston, IL, USA.ORCID http://orcid.org/0009-0000-1278-498X
Assa MagassaDepartment of Chemistry, Northwestern University, Evanston, IL, USA.ORCID http://orcid.org/0000-0001-6082-0324
Miguel A CamposDepartment of Chemistry, Northwestern University, Evanston, IL, USA.
Alana G CaldwellDepartment of Chemistry, Northwestern University, Evanston, IL, USA.
Felicia KoDepartment of Chemistry, Northwestern University, Evanston, IL, USA.ORCID http://orcid.org/0009-0008-2679-3578
Xiaoyu ZhangDepartment of Chemistry, Northwestern University, Evanston, IL, USA. zhang@northwestern.edu.ORCID http://orcid.org/0000-0002-0951-9664

Funding

Chemistry of Life Processes Predoctoral Training ProgramT32GM105538 · NIGMS · NORTHWESTERN UNIVERSITY · PI KELLEHER, NEIL L · 2013 to 2022
$2.7M
Chemistry of Life Processes Predoctoral Training ProgramT32GM149439 · NIGMS · NORTHWESTERN UNIVERSITY · PI NEIL L KELLEHER · 2023 to 2026
$1.6M
Discovery of small molecule-mediated protein degradation pathways in human cancerR00CA248715 · NCI · NORTHWESTERN UNIVERSITY · PI ZHANG, XIAOYU · 2022 to 2024
$747k
Damon Runyon Cancer Research Foundation (Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation) DFS-53-22NCI NIH HHS R00 CA248715NIGMS NIH HHS T32 GM105538NIGMS NIH HHS T32 GM149439U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R00CA248715U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32GM105538U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32GM149439
6 · The paper itself

Abstract

Targeted protein degradation (TPD) represents a potent chemical biology paradigm that leverages the cellular degradation machinery to pharmacologically eliminate specific proteins of interest. Although multiple E3 ligases have been discovered to facilitate TPD, there exists a compelling requirement to diversify the pool of E3 ligases available for such applications. Here we describe a clustered regularly interspaced short palindromic repeats (CRISPR)-based transcriptional activation screen focused on human E3 ligases, with the goal of identifying E3 ligases that can facilitate heterobifunctional compound-mediated target degradation. Through this approach, we identified a candidate proteolysis-targeting chimera (PROTAC), 22-SLF, that induces the degradation of FK506-binding protein 12 when the transcription of FBXO22 gene is activated. Subsequent mechanistic investigations revealed that 22-SLF interacts with C227 and/or C228 in F-box protein 22 (FBXO22) to achieve target degradation. Lastly, we demonstrated the versatility of FBXO22-based PROTACs by effectively degrading additional endogenous proteins, including bromodomain-containing protein 4 and the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion protein.

Indexed as

F-Box ProteinsProteolysisClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsHEK293 CellsHumansReceptors, Cytoplasmic and NuclearTranscriptional ActivationUbiquitin-Protein LigasesF-Box ProteinsFBXO22 protein, humanReceptors, Cytoplasmic and NuclearUbiquitin-Protein Ligases

Identifiers

PMID38965383
PMCPMC11581908

What OpenQuestion holds

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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.