Chemical induction of the interaction between AIMP2-DX2 and Siah1 to enhance ubiquitination
Citations

WEB OF SCIENCE

2
Citations

SCOPUS

2

초록

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. © 2024 Elsevier Ltd

키워드

AIMP2-DX2allosteric modulationand molecular dockingSiah1small moleculeubiquitinationPROTEIN-PROTEIN INTERACTIONSRNA SYNTHETASE COMPLEXSPLICING VARIANTSTABILIZATIONAIMP2/P38SCAFFOLD
제목
Chemical induction of the interaction between AIMP2-DX2 and Siah1 to enhance ubiquitination
저자
Kim, Dae GyuKim, MinkyoungGoo, Ja-ilKong, JiwonHarmalkar, Dipesh S.Lu, QiliSivaraman, AneeshNada, HossamGodesi, SreenivasuluLee, HwayoungSong, Mo EunSong, EunjooHan, Kang-HyunKim, WoojinKim, PilhanChoi, Won JunLee, Chang HoonLee, SunkyungChoi, YongseokKim, SunghoonLee, Kyeong
DOI
10.1016/j.chembiol.2024.08.004
발행일
2024-11
유형
Article
저널명
Cell Chemical Biology
31
11
페이지
1958 ~ 1968.e8