Ubiquitination-deubiquitination of a master transcriptional repressor that acts as a tumor suppressor or oncogene in diverse types of cancers, the RE-1 silencing transcription factor (REST) or neuron-restrictive silencer factor (NRSF), controls levels of this protein in cancer, and abnormal upregulation of REST has been found in medulloblastoma, neuroblastoma, and glioblastoma (Huang and Bao, 2012). This evidence concerns the gene REST and cancer.