Tumor Suppressors
Tumor suppressor genes are involved in inhibition of cell proliferation. Mutations that decrease the activity of tumor suppressor genes result in increased cell proliferation. In humans and other mammals, tumor suppressors include the retinoblastoma (Rb) and p53 proteins. Tumor suppressors have also been discovered in lower animals such as Drosophila, in which the Discs-Large (Dlg) and Hyperplastic Discs (Hyd) proteins inhibit hyperplasia of undifferentiated epithelial cells in developing imaginal discs. The importance of tumor suppressor genes and oncogenes in the development of cancer is demonstrated by the fact that about 75% of colorectal cancers have inactivating mutations in the p53 gene and about 50% have a hyper-activating mutation in a ras family oncogene.
Tumor supressor genes often act as gatekeepers. Normally, the gatekeeper is responsible for maintaining a balance of cell division, growth arrest, and death. External signals may activate or inactivate the gatekeeper, or alter its location within the cell. In some cases, inactivation of the gatekeeper is necessary for cell proliferation, and activation is necessary for cell growth arrest and differentiation. In other cases, the situation is reversed. Proteins that interact with the gatekeeper modify its activity or intracellular location to provide the appropriate response to external signals at any stage in the cell’s development.