NEDD8:AcM-UBE2M binds CUL9:RBX1 ubiquitin ligase complex

CUL9 (also known as PARC for p53-associated PARkin-like cytoplasmic protein) is an atypical cullin that has been shown to form a ubiquitin ligase complex with RBX1, although other components of the putative CRL9 complex have not yet been identified (Skaar et al, 2007; Li et al, 2014). CUL9:RBX1 is neddylated in vivo, likely through the UBE2M E2 although this hasn't been directly demonstrated (Skaar et al, 2007). <br>CUL9 is 60% identical to CUL7, another atypical mammalian cullin family member, but more distantly related to CUL1, 2, 3, 4A,4B and 5. CUL9 and CUL7 have been shown to form a heterodimer in vivo, and both interact with p53 (Skaar et al, 2007; Andrews et al, 2006; Nikolaev et al, 2003). CUL9 ubiquitinates BIRC5 (also known as Survivin), a protein with roles in cellular proliferation and inhibition of apoptosis. CUL9-mediated ubiquitination of BIRC5 is inhibited by the 3M complex, which consists of CUL7, CCDC8 and OBSL1 (Li et al, 2014).

CUL9，亦称为p53相关PARkin样细胞质蛋白（PARC），是一种非典型的Cullin蛋白，研究表明其能与RBX1形成泛素连接酶复合物，尽管CRL9假想复合物的其他组分尚未被鉴定（Skaar等，2007；Li等，2014）。CUL9:RBX1在体内被N-乙酰化，很可能通过UBE2M E2进行，尽管这一过程尚未得到直接证实（Skaar等，2007）。CUL9与CUL7（另一种非典型的哺乳动物Cullin家族成员）具有60%的同源性，但与CUL1、2、3、4A、4B和5的关系较为疏远。CUL9和CUL7在体内已被证实形成异源二聚体，并且两者均与p53相互作用（Skaar等，2007；Andrews等，2006；Nikolaev等，2003）。CUL9对BIRC5（也称为Survivin）进行泛素化，Survivin在细胞增殖和凋亡抑制中发挥作用。CUL9介导的BIRC5泛素化过程受到由CUL7、CCDC8和OBSL1组成的3M复合物的抑制（Li等，2014）。