Putting Cancer to REST

Although previous work has shown that either increasing or decreasing the level of repressor element-1-silencing transcription factor can induce tumors, it was unclear how to go about targeting or modulating the zinc-finger DNA-binding protein. Two papers published in Nature separately describe the discovery of an E3 ubiquitin ligase that mediates the degradation of the transcription factor in a variety of cell types. Thus, targeting the ligase might be one strategy for modulating cellular levels of repressor element-1-silencing transcription factor and treating cancer.

Repressor element-1-silencing transcription factor (REST) has many functions: it is a transcriptional repressor in normal neuronal development,¹an oncogene when overexpressed in neural stem cells²and a tumor suppressor in epithelial cells.³ Thus, excessively high or low levels of the protein's expression can result in cancer, depending on the cell type...