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Updated: Oct 30, 2025

Growth-based Determination and Biochemical Confirmation of Genetic Requirements for Protein Degradation in Saccharomyces cerevisiae
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Hydrophobic Tagging-Mediated Degradation of Transcription Coactivator SRC-1

So Ra Choi1, Hee Myeong Wang1, Min Hyeon Shin1,2

  • 1Department of Chemistry and Division of Advanced Material Science, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea.

International Journal of Molecular Sciences
|July 2, 2021
PubMed

Insights

Scientists developed a novel Steroid Receptor Coactivator-1 (SRC-1) degrader to target and reduce SRC-1 levels, effectively suppressing cancer cell migration and invasion. This breakthrough offers a promising therapeutic strategy for combating cancer metastasis.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Steroid receptor coactivator-1 (SRC-1) is crucial for signaling pathways and nuclear receptor function.
  • Elevated SRC-1 activity correlates with cancer metastasis and progression, making it a therapeutic target.

Purpose of the Study:

  • To develop a novel SRC-1 degrader for targeted degradation of cellular SRC-1.
  • To investigate the efficacy of a hydrophobic-tagged chimeric molecule in reducing SRC-1 levels and inhibiting cancer cell invasion.

Main Methods:

  • Design and synthesis of a novel SRC-1 degrader molecule.
  • Utilizing a selective SRC-1 ligand and a bulky hydrophobic group to induce proteasomal degradation.
  • Assessing the impact of the degrader on cellular SRC-1 levels, cancer cell migration, and invasion.

Main Results:

  • The developed SRC-1 degrader significantly reduced cellular SRC-1 levels.
  • The hydrophobic-tagged molecule effectively suppressed cancer cell migration and invasion.
  • The mechanism involves mimicking denatured proteins to trigger chaperone-mediated degradation via the ubiquitin-proteasome system (UPS).

Conclusions:

  • The novel SRC-1 degrader represents a new therapeutic approach for targeting cancer metastasis.
  • The hydrophobic tagging strategy shows potential for developing enhanced peptide-based protein degraders.
  • This approach offers a promising avenue for cancer therapy by targeting SRC-1 activity.
Keywords:
PROTACsSRC-1 transcriptional coactivatorcancer metastasishydrophobic taggingproteasomal degradationubiquitinationubiquitin–proteasome system

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