Fbxo45 facilitates pancreatic carcinoma progression by targeting USP49 for ubiquitination and degradation

• DOI: 10.1038/s41419-022-04675-2
• Publication Date: 2022-03-12T08:05:48Z
• Authors: Linhui Wu; Ke Yu; Kai Chen; Xuelian Zhu; Zheng Yang; Qi Wang; Junjie Gao; Yingying Wang; Tong Cao; Hui Xu; Xueshan Pan; Lixia Wang; Jun Xia; Yuyun Li; Zhiwei Peter Wang; Jia Ma
• Keywords: F-box protein

Abstract Fbxo45, a conserved F-box protein, comprises of an atypical SKP1, CUL1, protein (SCF) ubiquitin ligase complex that promotes tumorigenesis and development. However, the biological function molecular mechanisms Fbxo45 involved in pancreatic carcinogenesis are ambiguous. We conducted several approaches, including transfection, coIP, real-time polymerase chain reaction (RT-PCR), Western blotting, assays, animal studies, to explore role cancer. Here, we report USP49 stability is governed by Fbxo45-mediated ubiquitination enhanced absence Fbxo45. Moreover, binds short consensus sequence through its SPRY domain. Furthermore, degradation NEK6 kinase. Functionally, increases cell viability motility capacity targeting cancer cells. Xenograft mouse experiments demonstrated ectopic expression tumor growth mice overexpression inhibited vivo. Notably, was negatively associated with tissues. serves as oncoprotein facilitate oncogenesis regulating suppressor