AI Article Synopsis
- AIMP2-DX2 (DX2) is a variant of a protein linked to cancer, and reducing its levels can help stop tumor growth.
- Researchers found that a compound called SDL01 enhances the interaction between DX2 and another protein, Siah1, promoting DX2's degradation.
- SDL01 binds to a specific area on DX2, causing a change in its shape that strengthens its interaction with Siah1, showing that drug-induced changes can alter protein interactions.*
Article 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.
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| http://dx.doi.org/10.1016/j.chembiol.2024.08.004 | DOI Listing |
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