Ubiquitination and deubiquitination of REST and its roles in cancers

REST/NRSF (the RE-1 silencing transcription factor or neuron-restrictive silencer factor) was originally identified as a transcriptional repressor of a number of neuronal-specific genes in neural stem cells and non-neuronal cells. REST functions as a master regulator in the maintenance of neural stem cells. During tumorigenesis, REST shows opposing roles in different type of cells. In human epithelial cancers such as colon cancer, REST acts as a tumor suppressor. In contrast, REST plays an oncogenic role in the development of brain tumors and other cancers. Abnormal upregulation of REST has been found in medulloblastoma, neuroblastoma and glioblastoma (GBM). Recent studies in GBMs suggest that REST exerts its oncogenic function by maintaining self-renewal potential of glioma stem cells (GSCs).