Regulatory roles of tumor‐suppressor proteins and noncoding RNA in cancer and normal cell functions

We describe a mechanism for reversible regulation of gene transcription, mediated by a family of tumor‐suppressor proteins (TSP) containing a DNA‐binding domain (DBD) that binds to a gene and represses transcription, and RNA‐binding domains (RBDs) that bind RNA, usually a noncoding RNA (ncRNA), forming a TSP/RNA complex that releases the TSP from a gene and reverses repression. This mechanism appears to be involved in the regulation of embryogenesis, oncogenesis, and steroidogenesis. Embryonic cells express high levels of RNA that bind to a TSP and prevent repression of proto‐oncogenes that drive cell proliferation. The level of the RNA subsequently decreases in most differentiating cells, enabling a TSP to repress proto‐oncogenes and stop cell proliferation. Oncogenesis can result when the level of the RNA fails to decrease in a proliferating cell or increases in a differentiated cell. This mechanism also regulates transcription of P450scc , the first gene in the steroidogenic pathway. © 2007 Wiley‐Liss, Inc.