Targeted Inhibition of the NCOA1/STAT6 Protein-Protein Interaction
SCIE
SCOPUS
- Title
- Targeted Inhibition of the NCOA1/STAT6 Protein-Protein Interaction
- Authors
- Lee, Yeongju; Yoon, Heeseok; Hwang, Sung-Min; Shin, Min-Kyung; Lee, Ji Hoon; Oh, Misook; Im, Sin-Hyeog; Song, Jaeyoung; Lim, Hyun-Suk
- Date Issued
- 2017-11
- Publisher
- AMER CHEMICAL SOC
- 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.
- Keywords
- TRANSCRIPTION FACTOR; COACTIVATOR INTERACTION; SIGNAL TRANSDUCER; STAT6; MODULATORS; ACTIVATOR; PEPTIDES; MOLECULE; DOMAIN; HELIX
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/50467
- DOI
- 10.1021/jacs.7b08972
- ISSN
- 0002-7863
- Article Type
- Article
- Citation
- JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 139, no. 45, page. 16056 - 16059, 2017-11
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