CRL4B catalyzes H2AK119 monoubiquitination and coordinates with PRC2 to promote tumorigenesis

Huili Hu; Yang Yang; Qinghong Ji; Wei Zhao; Baichun Jiang; Ruiqiong Liu; Jupeng Yuan; Qiao Liu; Xi Li; Yongxin Zou; Changshun Shao; Yongfeng Shang; Yan Wang; Yaoqin Gong

doi:10.1016/j.ccr.2012.10.024

CRL4B catalyzes H2AK119 monoubiquitination and coordinates with PRC2 to promote tumorigenesis

Cancer Cell. 2012 Dec 11;22(6):781-95. doi: 10.1016/j.ccr.2012.10.024.

Authors

Huili Hu¹, Yang Yang, Qinghong Ji, Wei Zhao, Baichun Jiang, Ruiqiong Liu, Jupeng Yuan, Qiao Liu, Xi Li, Yongxin Zou, Changshun Shao, Yongfeng Shang, Yan Wang, Yaoqin Gong

Affiliation

¹ Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China.

PMID: 23238014
DOI: 10.1016/j.ccr.2012.10.024

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Cell Movement / genetics
Cell Transformation, Neoplastic / genetics
Cell Transformation, Neoplastic / metabolism*
Cell Transformation, Neoplastic / pathology
Cullin Proteins / genetics
Cullin Proteins / metabolism*
Cyclin-Dependent Kinase Inhibitor p16 / genetics
Cyclin-Dependent Kinase Inhibitor p16 / metabolism
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Esophageal Neoplasms / genetics
Esophageal Neoplasms / metabolism
Esophageal Neoplasms / pathology*
Female
Histones / genetics
Histones / metabolism
Humans
Male
Methylation
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
PTEN Phosphohydrolase / genetics
PTEN Phosphohydrolase / metabolism
Polycomb Repressive Complex 2 / genetics
Polycomb Repressive Complex 2 / metabolism*
Transcription, Genetic
Transplantation, Heterologous
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / metabolism
Ubiquitination*
Up-Regulation

Substances

CUL4B protein, human
Cullin Proteins
Cyclin-Dependent Kinase Inhibitor p16
DNA-Binding Proteins
Histones
Polycomb Repressive Complex 2
Ubiquitin-Protein Ligases
PTEN Phosphohydrolase
PTEN protein, human

Associated data

GEO/GSE41639