Small RING Finger Proteins RBX1 and RBX2 of SCF E3 Ubiquitin Ligases: The Role in Cancer and as Cancer Targets.
Small RING Finger Proteins RBX1 and RBX2 of SCF E3 Ubiquitin Ligases: The Role in Cancer and as Cancer Targets.
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DOI：
10.1177/1947601910382776
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发表时间：
2010-07
期刊：
影响因子：
--
通讯作者：
Sun Y
中科院分区：
文献类型：
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作者：
Wei D;Sun Y
SCF(Skp1-Cullins-F box Proteins，Skp1-Cullins-F box Proteins，Skp1-Cullins-F box Proteins)，又称CRL(Cullin-Based Ring Ligase)，是E3泛素连接酶家族中最大的一个家族，它介导约20%的泛素化蛋白底物参与26S蛋白酶体的降解。通过促进许多关键调节蛋白的及时降解，SCF E3连接酶控制着许多细胞过程；它的功能障碍导致了包括癌症在内的许多人类疾病。SCF复合体的环组分由两个家族成员组成：RBX1(环盒蛋白-1)和RBX2/ROC2(也称为SAG，对凋亡基因敏感)，这两个成员对SCF的催化活性都是必不可少的。RBX1和RBX2在从酵母到人类的进化过程中都是保守的，在小鼠胚胎发育过程中发挥着重要作用。此外，RBX1和RBX2在多种人类肿瘤组织中都过表达，是癌细胞生长和存活所必需的。在本文中，我们将讨论两个环家族成员的异同，它们对SCF E3连接酶活性的调节，以及它们在发育、癌细胞存活和皮肤癌发生中的作用，并简要讨论RBX-SCF E3连接酶作为癌症靶点和最近发现的SCF E3连接酶小分子抑制剂作为一类新的抗癌药物。
The SCF (Skp1-Cullins-F box proteins), also known as CRL (Cullin-based RING ligase), is the largest family of E3 ubiquitin ligases that mediate ~20% ubiquitinated protein substrates for 26S proteasome degradation. Through promoting timely degradation of many key regulatory proteins, SCF E3 ligase controls numerous cellular processes; its dysfunction contributes to a number of human diseases, including cancer. The RING component of SCF complex consists of two family members, RBX1 (RING box protein-1), also known as ROC1 (Regulator of Cullins) and RBX2/ROC2 (also known as SAG, Sensitive to Apoptosis Gene), both of which are essential for the catalytic activity of SCF. RBX1 and RBX2 are evolutionarily conserved from yeast to humans and play an essential role during mouse embryonic development. Moreover, RBX1 and RBX2 are both overexpressed in multiple human cancer tissues and required for the growth and survival of cancer cells. In this review, we will discuss the similarities and differences between two RING family members, their regulation of SCF E3 ligase activity, and their role in development, cancer cell survival and skin carcinogenesis, along with a brief discussion of RBX-SCF E3 ligases as the cancer targets and a recently discovered small molecule inhibitor of SCF E3 ligases as a novel class of anticancer drugs.