Notes

Writings about various topics and discussion worthy proteins

P53

monitors and responds to the health of the cell's DNA, acting as a tumor supressor

Created on

The protein, P53 acts as a signaling hub, initiating transcription for a number of downstream pathways under particular conditions. P53 is one of the most well-studied human genes, mostly for its ability to act as a cancer suppressor. The protein collects information about the cell’s state, particularly information regarding the integrity of the cell’s DNA, and acts on that information by turning on other proteins that may respond to the cell’s state. If P53 is mutated, the cell may have difficulty in noticing or responding to situations that threaten the integrity of the cell’s DNA.

P53 contains two domains that activate transcription, a dna-binding domain, a nuclear localization signal, and a tetramerization domain. Together, these domains ensure P53 is in the nucleus where it is useful, collect signals from other proteins in the cell, and can activate particular downstream pathways in response to those signals. P53 collects signals that are particularly important including DNA-repair, DNA-damage recognition, initiating programmed cell death (apoptosis), and triggering senescence in old cells.

Cancer

Mutations in the dna-binding domain are strongly associated with cancer, as they prevent a cell from properly responding to internal signals. If P53 cannot find or bind to the correct DNA sequence, it cannot turn on the proteins it should in order to respond to a particular signal. One of the more important signals a cell must respond to in order to prevent cancer is the signal to undergo apoptosis - for the cell to destroy itself if it notices it has been damaged beyond repair. If P53 can not properly activate apoptosis pathways, a damaged cell may continue to operate - oftentimes becoming uncontrollably disconnected from its original role in the organism, aka cancerous.

Elephants (with a lot more cells than a human), do not seem to get cancer at a rate proportional to the number of cells they have. Elephants have 20 copies of the DNA that encodes for P53 in their genome [1], possibly allowing for redundancy over the course of the animal’s life were one of the copies of DNA to be damaged. Having multiple copies of P53 is likely at least a partial solution to Peto’s paradox.

Vaccination

The protein E6 (E6 type 16 & E6 type 18), which is expressed by Human Papilloma Virus (HPV), inactivates P53. E6 has many strategies that simultaneously mark P53 for immediate degradation, confuse P53’s proper response to DNA-damage, and destroy other proteins that help P53 signal for a response to DNA-damage. By disabling P53, the virus shields itself from notice while it integrates its viral DNA into the cell’s DNA without triggering the expected DNA-damage response [2]. Once infected with HPV, cells no longer properly respond to important signals and become cancerous at a much-increased rate. Vaccinations for HPV prevent cells from being infected by the virus which prevents cells from having their P53 proteins be inactivated, thus preserving the cells’ ability to properly respond to information about their DNA’s state, and ultimately prevents the virus from significantly increasing the chance for the cell to become cancerous.

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