What role does p53 have in controlling cell division?

Answer 1

I will try to summarize my PhD thesis (on p53 regulation and cell cycle) of 320 pages in a few sentences.

p53 is a umor suppressor protein. That is a protein whose role is to slow down or arrest growth and proliferation, but also push the organism to remove cells damaged by the environment. p53 achieves all this mainly through downstream genes (but not lnly!). Low levels of p53 protein are transcribed/translated all the time, but the protein has a short half-life of 20min, if not stabilized by post-translational modifications, such as phosphorylation. The sites in the N-terminal domain (S15, S20, T18...), targets of ATM and ATR kinases, stabilize the protein by inhibiting its degradation through the proteasome pathway. p53 also presents multiple phosphorylation sites at its C-terminal domain (S315, S375, S392, among others). The kinases that causes phosphorylation at these sites are activated by DNA damage and environment stress and lead to activation of p53 in its properties of binding to the DNA. Upon cell damage, then, by binding to the DNA (as specific consensus sequences), p53 facilitates the transcription of genes involved in cell cycle progression (mostly p21), DNA repair (gadd45) and apoptosis (Bax). p21, also called Waf1 and Cip1, is an inhibitor of cyclin-dependent kinases: its major targets are cdk2-Cyclin E, cdk2-Cyclin A and cdc2-CyclinB. By binding to these complexes, p21 inactivates them and blocks the progression through the cell cycle (activation of checkpoints). The inhibition of the first 2 complexes leads to the G1/S checkpoint, whereas blocking cdc2-Cyclin B causes the G2/M checkpoint. These checkpoints are activated in case of damage and give the DNA the opportunity of repairing the damage. If this is not possible, then the proteins involved in apoptosis will take the lead (Bax is a pro-apoptotic protein) and push the cell to commit suicide through porgrammed cell death.

That of p53 mutations and cancer is a very broad field that could take pages to cover. Let´s just say that p53 is mutated in more than 50% of solid tumors. These mutations lay mostly in its central domain, which is responsible of binding to the DNA and activating downstream genes. Therefore in case of mutations, p21 and Bax, among others cannot be transcribed by p53 and the cell will not arrest proliferation or die of apoptosis in case of damage. Hence, it will be able to proliferate and expand (clone expansion) and spread its "damage" to daughter cells.

Hope it is not too much information

Answer 2

The gene of p53 makes the protein p53. p53 stimulates DNA to make the protein p21. p21 interacts with cdk2, a protein which stimulates cell division. BUT! the interaction of p21 which is made by the effect of p53, with cdk2 stops the cell division. if the p53 gene gets a damage, it will result in cancer! I hope you got the answer!

Answer 3

Normal p53 inhibits proliferation. When p53 is deactivated by mutations cells will proliferate uncontrollably and you get cancer.

Answer 4

it's the Protooncogene...It Turns the "On" on. lol.

Here, Think of it like this:
Protooncogenes = Gas Pedal
Tumor Suppressor Genes = Brakes.
Now, p53 is like Flooring the Gas Pedal !! =)