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면역 미생물 공생 연구단
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Targeted Inhibition of the NCOA1/STAT6 Protein-Protein Interaction

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Title
Targeted Inhibition of the NCOA1/STAT6 Protein-Protein Interaction
Author(s)
Yeongju Lee; Heeseok Yoon; Sung-Min Hwang; Min-Kyung Shin; Ji Hoon Lee; Misook Oh; Sin-Hyeog Im; Jaeyoung Song; Hyun-Suk Lim
Publication Date
2017-11
Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v.139, no.45, pp.16056 - 16059
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 h elical 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. © 2017 American Chemical Society
URI
https://pr.ibs.re.kr/handle/8788114/4159
ISSN
0002-7863
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
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