Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China.
Cancer Cell. 2012 Dec 11;22(6):781-95. doi: 10.1016/j.ccr.2012.10.024.
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.
我们曾报道 Cullin4B-Ring E3 连接酶复合物（CRL4B）与多梳抑制复合物 2（PRC2）在物理上相关。我们表明，CRL4B 通过促进 H2AK119 单泛素化具有内在的转录抑制活性。Cul4b 的缺失或 CRL4B 的主要成分 CUL4B 的耗竭不仅导致 H2AK119 单泛素化的丧失，而且导致 H3K27 三甲基化的丧失，导致细胞生长和迁移所必需的靶基因的去抑制。我们证明 CUL4B 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明显上调。我们的数据表明 CUL4B 促进肿瘤发生，支持将 CUL4B 作为癌症治疗的靶标进行研究。
