UTP11 deficiency suppresses cancer development via nucleolar stress and ferroptosis

• DOI: 10.1016/j.redox.2023.102705
• Publication Date: 2023-04-21T17:06:23Z
• Authors: Yu Gan; Jun Deng; Qian Hao; Yingdan Huang; Tao Han; Jin-Guo Xu; Min Zhao; Litong Yao; Yingying Xu; Jianping Xiong; Hua Lu; Chunmeng Wang; Jiaxiang Chen; Xiang Zhou
• Keywords: ribosome biogenesis; Ribosomal protein

The eukaryotic ribosome is essential for cancer cell survival. Perturbation of biogenesis induces nucleolar stress or ribosomal stress, which restrains growth, as rapidly proliferating cells need more active biogenesis. In this study, we found that UTP11 plays an important role in the biosynthesis 18S RNAs (rRNA) by binding to pre-rRNA processing factor, MPP10. overexpressed human cancers and associated with poor prognoses. Interestingly, depletion inhibits growth vitro vivo through p53-depedednt -independent mechanisms, whereas overexpression promotes progression. On one hand, ablation impedes rRNA trigger thereby preventing MDM2-mediated p53 ubiquitination degradation proteins, RPL5 RPL11. other deficiency represses expression SLC7A11 promoting decay NRF2 mRNA, resulting reduced levels glutathione (GSH) enhanced ferroptosis. Altogether, our study uncovers a critical maintaining survival depleting leads p53-dependent arrest p53-independent