HSP90 regulates dCK stability and inhibits ionizing radiation-induced ferroptosis in cervical cancer cells

Le résumé fourni par la source

Cervical squamous cell carcinoma (CESC) is one of the most common cancers in women, and radiotherapy has been used as a primary treatment. However, its efficacy is limited by intrinsic and acquired radiation resistance. Our previous study demonstrated that Deoxycytidine kinase (dCK) inhibits ionizing radiation (IR)-induced cell death, including apoptosis and mitotic catastrophe, and dCK is a HSP90-interacting protein by mass spectrometry and co-immunoprecipitation assay. In the present study, we found that dCK inhibited IR-induced ferroptosis by increasing the activity and stability of SLC7A11. Using the E3 ubiquitin ligase database (UbiBrowser), we predicted NEDD4L as a potential ubiquitin ligase of dCK, and WWP1/2 as potential ubiquitin ligases of NEDD4L, respectively. These predictions were subsequently verified through a ubiquitination IP assay. Our findings indicate that HSP90 regulates dCK stability by inhibiting NEDD4L through the recruitment of ubiquitin ligases WWP1/2. In summary, our study reveals the HSP90-WWP1/WWP2-NEDD4L-dCK-SLC7A11 axis as a critical regulator of IR-induced ferroptosis in HeLa cells. These findings provide valuable insights into potential strategies for the radiosensitization of cervical cancer.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.