The F-box protein FBXL18 promotes glioma progression by promoting K63-linked ubiquitination of Akt.
F-box proteins play pivotal roles in multiple cellular processes; however, little is known about their functions in glioma progression. In this study, we found that expression of the F-box and leucine-rich repeat protein 18 (FBXL18) is significantly upregulated in glioma tissues. Depletion of FBXL18 in glioma cells suppresses proliferation and anchorage-independent cell growth, and promotes apoptosis. We also demonstrate that depletion of FBXL18 significantly inhibits Akt activity and the phosphorylation of FOXO3a, which leads to upregulation of BCL2L11. Further mechanistic analyses indicate that FBXL18 promotes the K63-linked ubiquitination of Akt, which is required for its activation. Taken together, our results suggest that FBXL18 plays an oncogenic role through promoting K63-linked ubiquitination of Akt in glioma.
['Zhang|Jindong|J|', 'Yang|Zhifen|Z|', 'Ou|Jiayu|J|', 'Xia|Xiaojun|X|', 'Zhi|Feng|F|', 'Cui|Jun|J|']
D017209:Apoptosis D000072224:Bcl-2-Like Protein 11 D001932:Brain Neoplasms D045744:Cell Line, Tumor D049109:Cell Proliferation D018450:Disease Progression D044783:F-Box Proteins D015972:Gene Expression Regulation, Neoplastic D055785:Gene Knockdown Techniques D005910:Glioma D006801:Humans D008239:Lysine D019869:Phosphatidylinositol 3-Kinases D010766:Phosphorylation D051057:Proto-Oncogene Proteins c-akt D012333:RNA, Messenger D015398:Signal Transduction D054875:Ubiquitination D015854:Up-Regulation
FBXL18 glioma K63-linked ubiquitination Akt