Up to this point, we have considered what happens when mechanisms that promote cell division are inappropriately activated. Now let’s consider what happens when mechanisms that usually prevent cell cycle progression are removed.

Earlier, we discussed cell cycle checkpoints that halt the cell cycle until the cell is ready to divide. One of these checkpoints depends on the p53 protein, which normally arrests cell division in response to DNA damage. When the p53 protein is mutated or its function is inhibited, the cell can divide before the DNA damage is repaired. The result is that cells continue to divide in the presence of damaged DNA, leading to the accumulation of mutations that promote cell division. The p53 protein is mutated in many types of human cancer, highlighting its critical role in regulating the cell cycle.

The p53 protein is one example of a tumor suppressor. Tumor suppressors are proteins whose normal activities inhibit cell division. Some tumor suppressors participate in cell cycle checkpoints, as is the case for p53. Other tumor suppressors repress the expression of genes that promote cell division, while still others trigger cell death.

Tumor suppressors act in opposition to proto-oncogenes. Therefore, whether a cell divides or not depends on the activities of both proto-oncogenes and tumor suppressors: Proto-oncogenes must be turned on and tumor suppressors must be turned off. Given the importance of controlling cell division, it is not surprising that cells have two counterbalancing systems that must be in agreement before cell division takes place.

Quick Check 8 How do oncogenes differ from tumor suppressor genes?