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Regulating Cell Cycle

15 Oct

ImageCell cycle progression is regulated by the interplay of two major types of proteins. One protein promotes cell cycle progression (i.e. its effect is to push cells through the checkpoints); the other type of protein inhibits cell cycle progression. Together, these proteins establish a balance that permits cell cycle progression under typical conditions  – where there is no DNA damage. However, if there is DNA damage, proteins that sense this damage will turn on proteins that inhibit cell cycle and also those that are responsible for repairing the damage.

If all goes well and the damage is repaired, then the delaying proteins turn off and cell cycle is allowed to proceed. If the damage is NOT repaired, then the cell is instructed to commit suicide by apoptosis (cell death without inflammation).

The proteins that push cells through cycle are called proto-Oncogenes. The ones that inhibit cell cycle are called tumor suppressors.

That’s how things work when cell cycle is being regulated properly. But sometimes, the DNA damage may affect the genes for these two types of proteins specifically. When this happens, cell cycle regulation may be compromised. When that happens, cancer can develop.

Why? Because cancer is a disease of cell cycle regulation. The basic problem in cancer is that cells have ceased to have their cell cycle regulated properly and are dividing out of control. Remember, multicellular organisms like us thrive because we have delegated different behaviors to different cells / tissues / organs and all the cells are co-operating in a way that promotes the health of the individual organism ahead of the health of each individual cell.

So, what kind of mutation causes this to happen? Well, it depends upon which protein has been mutated. If pro to-oncogenes have a ‘gain of function’ mutation, this will make them work extra hard to push cells through cell cycle checkpoints – even when there are signals to prevent this. (Think of a gas pedal that gets stuck to the floor. It doesn’t matter if you hit the brakes, you’re still moving forward) If this same protein undergoes a ‘loss of function’ mutation, then the cell can never enter cell cycle and will probably die off.

Contra-wise, if tumor suppressor proteins have a ‘gain of function’ mutation, then cell cycle cannot proceed and the cell will probably die. (In a car analogy, tumor suppressor proteins are the brake pedal. If the break is always on, then you can never go forward. If the tumor suppressor protein has a ‘loss of function’ mutation, then cell cycle can never stop (our brakes are broken).

So, each type of protein has to have a specific type of mutation to lead to unregulated cell cycle.

Keep in mind, that the purpose of cell cycle regulation is to protect the integrity of the genome (all the DNA of the cell). If this regulation breaks, then more and more mutations can occur over time.

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Posted by on October 15, 2012 in Uncategorized

 

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