A novel protein–protein interaction between rsk3 and iκbα and a new binding inhibitor that suppresses breast cancer tumorigenesis

Hee Sub Yoon, Sung Hoon Choi, Jung Hyun Park, Jin Young Min, Ju Yong Hyon, Yeji Yang, Sejin Jung, Jae Young Kim, Nam Doo Kim, Ji Hoon Lee, Eun Hee Han, Sung Gil Chi, Young Ho Chung

Research output: Contribution to journalArticlepeer-review

Abstract

Multiple cancer-related biological processes are mediated by protein-protein interactions (PPIs). Through interactions with a variety of factors, members of the ribosomal S6 kinase (RSK) family play roles in cell cycle progression and cell proliferation. In particular, RSK3 contributes to cancer viability, but the underlying mechanisms remain unknown. We performed a kinase library screen to find IκBα PPI binding partners and identified RSK3 as a novel IκBα binding partner using a cell-based distribution assay. In addition, we discovered a new PPI inhibitor using mammalian twohybrid (MTH) analysis. We assessed the antitumor effects of the new inhibitor using cell proliferation and colony formation assays and monitored the rate of cell death by FACS apoptosis assay. IκBα is phosphorylated by the active form of the RSK3 kinase. A small-molecule inhibitor that targets the RSK3/IκBα complex exhibited antitumor activity in breast cancer cells and increased their rate of apoptosis. RSK3 phosphorylation and RSK3/IκBα complex formation might be functionally important in breast tumorigenesis. The RSK3/IκBα-specific binding inhibitor identified in this study represents a lead compound for the development of new anticancer drugs.

Original languageEnglish
Article number2973
JournalCancers
Volume13
Issue number12
DOIs
Publication statusPublished - 2021 Jun 2

Keywords

  • Binding inhibition
  • Breast cancer
  • Cell-based unidentified protein interaction discovery (CUPID)
  • IκBα
  • Protein-protein interaction (PPI)
  • RSK3 (RPS6KA2)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'A novel protein–protein interaction between rsk3 and iκbα and a new binding inhibitor that suppresses breast cancer tumorigenesis'. Together they form a unique fingerprint.

Cite this