The F-box protein FBXL18 promotes glioma progression by promoting K63-linked ubiquitination of Akt.

ABSTRACT

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.