by Barnaby Meins

Created on: May 07, 2010

Tumor-suppressor genes are those that encode proteins which inhibit cell proliferation. Loss of one or more of these brakes contributes to the development of many cancers. Five broad classes of proteins are generally recognized as being encoded by tumor-suppressor genes, namely, intracellular proteins, receptors for secreted hormones, checkpoint-control proteins, apoptosis promoting proteins and DNA repair enzymes.

Intracellular proteins, such as p16 cyclin-kinase inhibitor, regulate or inhibit progression through a specific stage of the cell cycle. Receptors for secreted hormones, for example tumor-derived growth factor, function to inhibit cell proliferation. Checkpoint-control proteins are proteins that arrest the cell cycle if DNA is damaged or chromosomes are abnormal

The p53 gene may be one of the most important tumor-suppressor gene in human cancer because this tumor suppressor gene is mutated in about half of all human cancers. Mutations in the p53 gene allow cancer cells to survive and proliferate despite DNA damage. Its triple involvement in cell-cycle control, apoptosis, and in maintenance of genetic stability-all aspects of the fundamental role of the p53 protein in protecting the organism against cellular damage and disorder. p53 protein exerts its cell-cycle effects, in part at least, by binding to DNA and inducing the transcription of p21,a regulatory gene whose protein product binds to Cdk complexes required for entry into and progress through S-phase. p21 protein prevents the cell from entering S phase and replicating its DNA by blocking the kinase activity of these Cdk complexes.

p53 is not required for normal development in that its function is required only occasionally or in special circumstances. When normal cells are deprived of oxygen or exposed to treatments that damage DNA, such as ultraviolet light or gamma rays, they raise their concentration of p53 protein by reducing the normally rapid rate of degradation of the molecule. In these cases, the high level of p53 protein acts to limit the harm done. Depending on circumstances and severity of damage, p53 may either drive the damaged or mutant cell to commit suicide by apoptosis, a relatively harmless event for the multicellular organism or trigger a mechanism that bars the cell from dividing so long as the damage remains unrepaired. The protection provided by p53 is an important part of the reason why mutations that activate oncogenes such as Ras and Myc are not enough by themselves

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