title: F-box protein FBXO22 mediates polyubiquitination and degradation of KLF4 to promote hepatocellular carcinoma progression.
abstract: Kruppel-like factor 4 (KLF4), a member of the KLF family of transcription factors, has been considered as a crucial tumor suppressor in hepatocellular carcinoma (HCC). Using affinity purifications and mass spectrometry, we identified FBXO22, Cullin1 and SKP1 as interacting proteins of KLF4. We demonstrate that F-box only protein 22 (FBXO22) interacts with and thereby destabilizes KLF4 via polyubiquitination. As a result, FBXO22 could promote HCC cells proliferation both in vitro and in vivo. However, KLF4 deficiency largely blocked the proliferative roles of FBXO22. Importantly, FBXO22 expression was markedly increased in human HCC tissues, which was correlated with down-regulation of KLF4. Therefore, our results suggest that FBXO22 might be a major regulator of HCC development through direct degradation of KLF4.
authors.affiliation: Molecular Oncology Laboratory of Cancer Research Institute, the First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, 110001, China.|Institute of Pathology and Pathophysiology, Shenyang, 110001, China.
authors.forename: Shundong
authors.initials: S
authors.lastname: Dai
authors.affiliation: Department of Immunology and Biotherapy, Liaoning Cancer Hospital and Institute, Shenyang, 110042, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Guojiang
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Rheumatology, the First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Shenyi
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Molecular Oncology Laboratory of Cancer Research Institute, the First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Fandong
authors.initials: F
authors.lastname: Meng
authors.affiliation: Molecular Oncology Laboratory of Cancer Research Institute, the First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Molecular Oncology Laboratory of Cancer Research Institute, the First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Molecular Oncology Laboratory of Cancer Research Institute, the First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Youhong
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D018450:Disease Progression; D015536:Down-Regulation; D044783:F-Box Proteins / Q000378:metabolism*; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D047468:Immunoprecipitation; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D044783:F-Box Proteins; C561886:FBXO22 protein, human; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D018160:Receptors, Cytoplasmic and Nuclear; D044767:Ubiquitin-Protein Ligases
keywords: FBXO22; Kruppel-like factor 4; hepatocellular carcinoma; ubiquitination