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Chemical induction of the interaction between AIMP2-DX2 and Siah1 to enhance ubiquitination.
- Source :
-
Cell chemical biology [Cell Chem Biol] 2024 Sep 03. Date of Electronic Publication: 2024 Sep 03. - Publication Year :
- 2024
- Publisher :
- Ahead of Print
-
Abstract
- AIMP2-DX2 (hereafter DX2) is an oncogenic variant of aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) that mediates tumorigenic interactions with various factors involved in cancer. Reducing the levels of DX2 can effectively inhibit tumorigenesis. We previously reported that DX2 can be degraded through Siah1-mediated ubiquitination. In this study, we identified a compound, SDL01, which enhanced the interaction between DX2 and Siah1, thereby facilitating the ubiquitin-dependent degradation of DX2. SDL01 was found to bind to the pocket surrounding the N-terminal flexible region and GST domain of DX2, causing a conformational change that stabilized its interaction with Siah1. Our findings demonstrate that protein-protein interactions (PPIs) can be modulated through chemically induced conformational changes.<br />Competing Interests: Declaration of interests This work has been patented in 2020 under patent number (WO2020204548A1, worldwide applications).<br /> (Copyright © 2024 Elsevier Ltd. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 2451-9448
- Database :
- MEDLINE
- Journal :
- Cell chemical biology
- Publication Type :
- Academic Journal
- Accession number :
- 39260366
- Full Text :
- https://doi.org/10.1016/j.chembiol.2024.08.004