Related Experiment Video

Updated: Nov 10, 2025

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

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Inhibition of NUPR1-Karyopherin β1 Binding Increases Anticancer Drug Sensitivity

Chanhee Park1,2, Jiwon Oh3, Won Mo Lee1

  • 1Center for Metareceptome Research, College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak, Seoul 06974, Korea.

International Journal of Molecular Sciences
|April 3, 2021
PubMed
Abstract

Insights

Nuclear protein-1 (NUPR1) nuclear translocation is mediated by karyopherin β1 (KPNB1). Inhibiting this interaction with ATZ-502 shows synergistic anticancer effects and may offer a new therapeutic strategy.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Cancer Research

Background:

  • Nuclear protein-1 (NUPR1) is a transcription factor regulating cellular stress responses.
  • NUPR1 plays a role in cellular responses to stimuli like starvation and drugs.

Purpose of the Study:

  • To investigate the mechanism of NUPR1 nuclear translocation.
  • To explore the role of karyopherin β1 (KPNB1) in NUPR1 translocation.
  • To evaluate the therapeutic potential of inhibiting the NUPR1-KPNB1 interaction.

Main Methods:

  • Single-molecule binding assays and confocal microscopy were used to study NUPR1-KPNB1 interactions.
  • Gene expression profiling and cell cycle analysis assessed cellular effects of NUPR1-KPNB1 inhibition.
  • The aminothiazole ATZ-502 was used to inhibit the NUPR1-KPNB1 binding.

Main Results:

  • KPNB1 binds NUPR1 with high affinity (0.75 nM), an interaction blocked by ATZ-502.
  • ATZ-502 inhibited NUPR1 nuclear translocation in MDA-MB-231 cells following doxorubicin treatment.
  • Inhibiting NUPR1-KPNB1 binding resulted in synergistic anticancer effects (up to 19.6-fold) and downregulated NUPR1-related genes.

Conclusions:

  • NUPR1 nuclear translocation is dependent on binding to KPNB1.
  • Inhibiting the KPNB1-NUPR1 interaction presents a novel therapeutic strategy for cancer.
  • This approach may enhance drug efficacy and reduce side effects in cancer treatment.
Keywords:
KPNB1NUPR1combinationdrug sensitivityprotein binding

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