Transcriptional regulation by tumor suppressor genes

Several proteins that function as transcription factors play important roles in tumor suppression because they function as modulators of gene expression. P53, for example, activates the transcription of genes that are involved in growth suppression or apoptosis. The stability of p53 is greatly increased upon DNA damage, indicating its role in these processes. In contrast to p53, WT1 appears to function by repressing the transcription of a set of growth-inducing genes, such asEGR-1andPDGF A.The Rb protein, while not a transcription factor per se, modulates transcription by binding and inactivating transcription factors required for cell cycle progression. All three of these tumor suppressor genes are found to be mutated in a large variety of human tumors. The mutations in these genes often disrupt their transcriptional activities. Through their intrinsic ability to regulate a host of other genes involved in growth control, they can reorganize and redirect a cell’s fate. Thus, it is not surprising that loss of these genes by deletion or mutation is a common occurrence in tumorigenesis.