Regulation of cancer stem cells by RING finger ubiquitin ligases

Like normal stem cells, cancer stem cells (CSCs) are capable of self-renewal, either by symmetric or asymmetric cell division. They have the exclusive ability to reproduce malignant tumors indefinitely, and to confer resistance in response to radiation or chemotherapy. The ubiquitin modification system plays various roles in physiology and pathology. The key component for the specificity of this system is ubiquitin ligases (E3s). Of these E3s, the majority are RING finger proteins. Many RING finger E3s, such as the Cullin1-Skp1-F-box protein (SCF) E3s, CBL, BRCA1, MDM2 and von Hippel-Lindau tumour suppressor (VHL), are crucial in the regulation of cell-cycle progression and cell differentiation. As a result, many RING finger E3s are implicated in the positive and negative regulation of CSC maintenance. This review summarizes current knowledge in this research field.