OTUD4 promotes the progression of glioblastoma by deubiquitinating CDK1 and activating MAPK signaling pathway

• DOI: 10.1038/s41419-024-06569-x
• Publication Date: 2024-03-01T13:03:19Z
• Authors: Mingxin Ci; Gaichao Zhao; Chongyang Li; Ruochen Liu; Xiaosong Hu; Jun Pan; Yang Shen; Guanghui Zhang; Yongsen Li; Li Zhang; Ping Liang; Hongjuan Cui
• Keywords: Deubiquitinating enzyme

Abstract Glioblastoma, IDH-Wild type (GBM, CNS WHO Grade 4) is a highly heterogeneous and aggressive primary malignant brain tumor with high morbidity, mortality, poor patient prognosis. The global burden of GBM increasing notably due to limited treatment options, drug delivery problems, the lack characteristic molecular targets. OTU deubiquitinase 4 (OTUD4) potential predictive factor for several cancers such as breast cancer, liver lung cancer. However, its function in remains unknown. In this study, we found that expression OTUD4 positively associated prognosis patients. Moreover, provided vitro vivo evidence promotes proliferation invasion cells. Mechanism studies showed that, on one hand, directly interacts cyclin-dependent kinase 1 (CDK1) stabilizes CDK1 by removing K11, K29, K33-linked polyubiquitination. On other binds fibroblast growth receptor (FGFR1) reduces FGFR1’s K6 K27-linked polyubiquitination, thereby indirectly stabilizing CDK1, ultimately influencing activation downstream MAPK signaling pathway. Collectively, our results revealed progression via OTUD4-CDK1-MAPK axis, may be prospective therapeutic target treatment.