Targeted Inhibition of the NCOA1/STAT6 Protein-Protein Interaction

Yeongju Lee, Heeseok Yoon, Sung Min Hwang, Min Kyung Shin, Ji Hoon Lee, Misook Oh, Sin Hyeog Im, Jaeyoung Song, Hyun-Suk Lim

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The complex formation between transcription factors (TFs) and coactivator proteins is required for transcriptional activity, and thus disruption of aberrantly activated TF/coactivator interactions could be an attractive therapeutic strategy. However, modulation of such protein-protein interactions (PPIs) has proven challenging. Here we report a cell-permeable, proteolytically stable, stapled helical peptide directly targeting nuclear receptor coactivator 1 (NCOA1), a coactivator required for the transcriptional activity of signal transducer and activator of transcription 6 (STAT6). We demonstrate that this stapled peptide disrupts the NCOA1/STAT6 complex, thereby repressing STAT6-mediated transcription. Furthermore, we solved the first crystal structure of a stapled peptide in complex with NCOA1. The stapled peptide therefore represents an invaluable chemical probe for understanding the precise role of the NCOA1/STAT6 interaction and an excellent starting point for the development of a novel class of therapeutic agents.

Original languageEnglish (US)
Pages (from-to)16056-16059
Number of pages4
JournalJournal of the American Chemical Society
Volume139
Issue number45
DOIs
StatePublished - Nov 15 2017
Externally publishedYes

Fingerprint

Nuclear Receptor Coactivator 1
STAT6 Transcription Factor
STAT Transcription Factors
Transcription
Transducers
Peptides
Proteins
Transcription factors
Transcription Factors
Crystal structure
Modulation
Cytoplasmic and Nuclear Receptors
Therapeutics

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Targeted Inhibition of the NCOA1/STAT6 Protein-Protein Interaction. / Lee, Yeongju; Yoon, Heeseok; Hwang, Sung Min; Shin, Min Kyung; Lee, Ji Hoon; Oh, Misook; Im, Sin Hyeog; Song, Jaeyoung; Lim, Hyun-Suk.

In: Journal of the American Chemical Society, Vol. 139, No. 45, 15.11.2017, p. 16056-16059.

Research output: Contribution to journalArticle

Lee, Y, Yoon, H, Hwang, SM, Shin, MK, Lee, JH, Oh, M, Im, SH, Song, J & Lim, H-S 2017, 'Targeted Inhibition of the NCOA1/STAT6 Protein-Protein Interaction', Journal of the American Chemical Society, vol. 139, no. 45, pp. 16056-16059. https://doi.org/10.1021/jacs.7b08972
Lee, Yeongju ; Yoon, Heeseok ; Hwang, Sung Min ; Shin, Min Kyung ; Lee, Ji Hoon ; Oh, Misook ; Im, Sin Hyeog ; Song, Jaeyoung ; Lim, Hyun-Suk. / Targeted Inhibition of the NCOA1/STAT6 Protein-Protein Interaction. In: Journal of the American Chemical Society. 2017 ; Vol. 139, No. 45. pp. 16056-16059.
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