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在有丝分裂过程中，细胞复制染色体DNA，纺锤体将染色体拉开，并使其平均分配到两个子细胞中。这一过程出现问题会导致染色体数异常，进而引发癌症和其他疾病。RNF20/40复合物是一个重要的泛素连接酶，负责组蛋白H2B的单泛素化。 2016年8月25日，英国《自然·通讯》在线发表天津医科大学、中国科学院生物物理研究所、北京大学医学部的研究报告，发现RNF20/40复合物在有丝分裂过程中与马达蛋白Eg5互作，并且参与了纺锤体的装配。该研究通讯作者为宣成昊、尚永丰。 该研究显示，RNF20/40复合物能使Eg5单泛素化，增强其稳定性。RNF20/40缺失会导致纺锤体装配缺陷、细胞周期停滞和细胞凋亡。在活体内去除RNF20/40或Eg5，都能起到抑制乳腺癌的效果。 乳腺癌是女性中最常见、也最严重的恶性肿瘤之一，其发病率一直在不断增加。乳腺癌的发病与遗传有关，以40～60岁之间、绝经期前后的妇女发病率较高，仅约1～2%的乳腺患者是男性。这种恶性肿瘤通常发生在乳腺上皮组织，会严重影响女性的身心健康乃至危及生命。 该研究发现，人类乳腺癌RNF20/40和Eg5同时上调，而且Eg5高水平表达与乳腺癌患者生存情况差有关。该研究揭示了RNF20/40复合物的纺锤体装配功能，以及RNF20/40-Eg5通路在乳腺癌发生中的作用，这些蛋白质有望成为乳腺癌治疗的潜在靶标。 Nat Commun. 2016 Aug 25;7:12648. Ubiquitin ligase RNF20/40 facilitates spindle assembly and promotes breast carcinogenesis through stabilizing motor protein Eg5. Duan Y, Huo D, Gao J, Wu H, Ye Z, Liu Z, Zhang K, Shan L, Zhou X, Wang Y, Su D, Ding X, Shi L, Wang Y, Shang Y, Xuan C. Tianjin Medical University, Tianjin 300070, China; Tianjin Medical University General Hospital, Tianjin 300052, China; Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Peking University Health Science Center, Beijing 100191, China. Whether transcriptional regulators are functionally involved in mitosis is a fundamental question in cell biology. Here we report that the RNF20/40 complex, a major ubiquitin ligase catalysing histone H2B monoubiquitination, interacts with the motor protein Eg5 during mitosis and participates in spindle assembly. We show that the RNF20/40 complex monoubiquitinates and stabilizes Eg5. Loss of RNF20/40 results in spindle assembly defects, cell cycle arrest and apoptosis. Consistently, depletion of either RNF20/40 or Eg5 suppresses breast cancer in vivo. Significantly, RNF20/40 and Eg5 are concurrently upregulated in human breast carcinomas and high Eg5 expression is associated with poorer overall survival of patients with luminal A, or B, breast cancer. Our study uncovers an important spindle assembly role of the RNF20/40 complex, and implicates the RNF20/40-Eg5 axis in breast carcinogenesis, supporting the pursuit of these proteins as potential targets for breast cancer therapeutic interventions. PMID: 27557628 DOI: 10.1038/ncomms12648
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