CUL9:RBX1 ubiquitinates BIRC5

One defined target of CUL9 ubiquitin ligase is BIRC5 (also known as Survivin), which has roles in cellular proliferation, inhibition of apoptosis and maintenance of genome stability (Zhao et al, 2000; Watanabe, 2010). Deletion of CUL9 leads to polyploidy, abnormal nuclear morphology and DNA damage and is accompanied by an increase in survivin protein levels (Li et al, 2014). CUL9-mediated ubiquitination of BIRC5 is negatively regulated by the 3M complex, consisting of CUL7, CCDC8 and OBSL1 (Li et al, 2014; Yan et al, 2014). This CUL7-dependent inhibition of CUL9 ubiquitin ligase activity is promoted by heterodimerization between CUL7 and CUL9 (Li et al, 2014).

CUL9泛素连接酶所靶向的特定目标之一为BIRC5（亦称Survivin），其在细胞增殖、凋亡抑制及基因组稳定性维持等方面发挥着重要作用（Zhao等，2000；Watanabe，2010）。CUL9的缺失会导致多倍体现象、异常的核形态以及DNA损伤，并伴随Survivin蛋白水平的上升（Li等，2014）。CUL9介导的BIRC5泛素化过程受到由CUL7、CCDC8和OBSL1组成的3M复合体的负调控（Li等，2014；Yan等，2014）。这种依赖于CUL7的CUL9泛素连接酶活性抑制过程，通过CUL7与CUL9之间的异源二聚化得到促进（Li等，2014）。