title: CRL4B catalyzes H2AK119 monoubiquitination and coordinates with PRC2 to promote tumorigenesis.
abstract: We reported that Cullin4B-Ring E3 ligase complex (CRL4B) is physically associated with Polycomb-repressive complex 2 (PRC2). We showed that CRL4B possesses an intrinsic transcription repressive activity by promoting H2AK119 monoubiquitination. Ablation of Cul4b or depletion of CUL4B, the main component of CRL4B, resulted in loss of not only H2AK119 monoubiquitination but also H3K27 trimethylation, leading to derepression of target genes that are critically involved in cell growth and migration. We demonstrated that CUL4B promotes cell proliferation, invasion, and tumorigenesis in vitro and in vivo and found that its expression is markedly upregulated in various human cancers. Our data indicate that CUL4B promotes tumorigenesis, supporting the pursuit of CUL4B as a target for cancer therapy.
authors.affiliation: Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Huili
authors.initials: H
authors.lastname: Hu
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Ji
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Baichun
authors.initials: B
authors.lastname: Jiang
authors.forename: Ruiqiong
authors.initials: R
authors.lastname: Liu
authors.forename: Jupeng
authors.initials: J
authors.lastname: Yuan
authors.forename: Qiao
authors.initials: Q
authors.lastname: Liu
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Zou
authors.forename: Changshun
authors.initials: C
authors.lastname: Shao
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Shang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yaoqin
authors.initials: Y
authors.lastname: Gong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination; D015854:Up-Regulation
chemical_list: C517832:CUL4B protein, human; D044842:Cullin Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D006657:Histones; D063151:Polycomb Repressive Complex 2; D044767:Ubiquitin-Protein Ligases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human