Related Experiment Video

Updated: Aug 15, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

Photoproximity labeling of c-Myc reveals SLK as a cancer-specific co-regulator

Ryan R Milione1,2, Feifei Tong1,3, Kelsey L Wolfe2,4

  • 1Department of Chemistry, Wertheim UF Scripps, Jupiter, FL, USA.

Nature Chemical Biology
|August 14, 2026
PubMed

Insights

Researchers identified a new way to target cancer by finding protein interactions. They discovered that STE20-like kinase (SLK) stabilizes c-Myc, a key factor in tumor growth, offering a potential new therapeutic strategy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Transcription factors (TFs) are crucial in regulating cell states, but many are disordered and difficult to target directly with drugs.
  • Indirectly targeting molecules that modulate TF function presents a promising alternative for therapeutic intervention.

Purpose of the Study:

  • To develop a novel strategy for capturing cancer-specific protein-protein interactions.
  • To identify druggable vulnerabilities by analyzing the c-Myc interactome in healthy and cancerous prostate cells.

Main Methods:

  • Utilized context-dependent µMap photoproximity labeling for capturing protein interactions within intact nuclei.
  • Employed an intein-based method for catalyst conjugation.
  • Analyzed c-Myc interactomes in prostate cancer cells.

Main Results:

  • Identified STE20-like kinase (SLK) as a cancer-specific interactor that stabilizes c-Myc.
  • Demonstrated that SLK phosphorylates c-Myc at serine 329, counteracting GSK3β-dependent degradation.
  • Linked a specific SLK isoform, promoted by splicing changes, to c-Myc target gene expression and tumorigenesis across diverse tissues.

Conclusions:

  • The discovered SLK-c-Myc interaction represents a novel vulnerability in cancer.
  • This strategy of targeting TF-modulating proteins offers a new avenue for cancer therapy development.

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