Carfilzomib triggers cardiotoxicity by suppressing SENP1-mediated deSUMOylation of DDX17

作者：Sheng Wang, Jingjing Wang, Xin Li, Zhigao Dai, Tiantian Li, Yixuan Wang, Ziyi Peng, Mengqi Wang, Hao Cheng, Linchuang Jia, D Su, M. Qiao, Jingya Wang, Ying Xie, Jing Guo, Xiaozhi Liu, Tong Liu · 发表于：Acta Biochimica et Biophysica Sinica · 年份：2025 · DOI：10.3724/abbs.2025121 · 被引用次数：2 · 研究领域：Ubiquitin and proteasome pathways、Protein Degradation and Inhibitors、Multiple Myeloma Research and Treatments

cultured neonatal rat cardiomyocytes. Suppression of SENP1 exacerbates Cfz-induced injury and remodeling in cardiomyocytes by directly binding to and deconjugating the SUMO1-mediated SUMOylation of the RNA helicase DDX17. This process leads to a reduction in K-48 ubiquitin-linked polyubiquitination and degradation of DDX17, resulting in increased expressions of anti-apoptotic genes and maintenance of mitochondrial homeostasis. Therefore, the overexpression of SENP1 using AAV vectors alleviates Cfz-induced cardiotoxicity in mice. In summary, our findings reveal a previously unknown role of the SENP1-DDX17 axis in protecting against cardiotoxicity induced by Cfz, providing a potential foundation for developing therapeutic strategies to mitigate cardiac side effects in the clinical management of MM patients.