CRL4B Catalyzes H2AK119 Monoubiquitination and Coordinates with PRC2 to Promote Tumorigenesis
CRL4B Catalyzes H2AK119 Monoubiquitination and Coordinates with PRC2 to Promote Tumorigenesis
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CRL4B 催化 H2AK119 单泛素化并与 PRC2 协调促进肿瘤发生
DOI：
10.1016/j.ccr.2012.10.024
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发表时间：
2012-12-11
期刊：
影响因子：
50.3
通讯作者：
Gong, Yaoqin
中科院分区：
文献类型：
--
作者：
Hu, Huili;Yang, Yang;Gong, Yaoqin
我们报道了Cullin 4 B-环E3连接酶复合物（CRL 4 B）与Polycomb-阻遏复合物2（PRC 2）的物理结合。我们发现，CRL 4 B具有内在的转录抑制活性，通过促进H2 AK 119单泛素化。Cul 4 b的消融或CUL 4 B（CRL 4 B的主要组分）的消耗不仅导致H2 AK 119单泛素化的丧失，而且导致H3 K27三甲基化的丧失，从而导致关键参与细胞生长和迁移的靶基因的去阻遏。我们证明了CUL 4 B在体外和体内促进细胞增殖、侵袭和肿瘤发生，并发现其表达在各种人类癌症中显著上调。我们的数据表明，CUL 4 B促进肿瘤发生，支持CUL 4 B作为癌症治疗靶点的追求。
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.