title: 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.
authors.affiliation: Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China.|Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jindong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Clinical laboratory, Changsha Blood Center, Changsha, China.
authors.forename: Zhifen
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Ou
authors.affiliation: Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China.|State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Xia
authors.affiliation: Modern Medical Research Center, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhi
authors.affiliation: Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China.|Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cui
mesh_terms: D017209:Apoptosis; D000072224:Bcl-2-Like Protein 11 / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D044783:F-Box Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D054875:Ubiquitination; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000072224:Bcl-2-Like Protein 11; D044783:F-Box Proteins; D008239:Lysine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; C000606775:BCL2L11 protein, human; C000601116:FBXL18 protein, human
keywords: Akt; FBXL18; K63-linked ubiquitination; glioma