Small RING Finger Proteins RBX1 and RBX2 of SCF E3 Ubiquitin Ligases: The Role in Cancer and as Cancer Targets.

The SCF (Skp1-cullin-F-box proteins), also known as CRL (cullin-based RING ligase), is the largest family of E3 ubiquitin ligases that mediate approximately 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 2 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 2 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.