We know that we all start life as one single cell and that cell multiplies and then forms tissues, which form organs and organs form, well, us, this division is called growth!
Cell division is an intricate chemical dance, that is partly individual and partly community driven in a surrounding of ‘32.7 trillion cells in our body’. Errors, however, can occur within a cell and an individual set of DNA can get a typo which is called “Mutation”. Most of the time, cells recognise their mistake and shut their self-down; or the system just senses the cell and eliminates it. Unfortunately, enough mutation can by-pass which means the cell will divide recklessly. That one cell starts to multiply; at every multiplication, the incorrect set of DNA is passed along to the cell’s offspring. It may take weeks, months or even years after that one mistaken cell transforms, this is cancer.
There are many types of cancer, but in this essay, we are going to focus on p53 Cancer, which is not cancer but rather a tumour sprucer.
The p53 is a tumour sprucer gene; its activity stops the formation of tumours. This gene is located on the 17p13, ‘first discovered in 1979.’ (Moll and Petrenko, 2003)
the p53 protein is the product of p53 Gene, which P stands for protein and the 53 stands for the weight of the protein/ 53 KDa. It is located in almost all tissues, and is very unsubtle and degrades very quickly. This is also one of the most mutated gene in cancer.
‘p53 prevents neoplastic transformation, either by cell cycle arrest or by triggering apoptosis’ (molecular cancer research, 2003)
When there is a DNA damage, it triggers the expression of p53 gene and also increases the level of p53. This prevents the cell from entering the s phase of the cell cycle. An arrest takes place in the G1 phase, this allows time for the DNA repair to take place. It also induces p3 genes, which helps with the repair of the DNA; unless the damage is very extensive.
Once the DNA is repaired, the p53 degrades. If there is no p53, that means the cell cycle can continue and there will be no arrest. But if the DNA damage is extensive and cannot be repaired by the p53. This would either cause a permanent arrest, senescence or it may cause a apoptosis.
The function of the p53 is that whenever there is a damage to the DNA, the p53 comes to the rescue. This also means that it conserves the stability of the Genome and therefore sometimes, the p53 is referred to as the guardian of the Genome.
Understanding regulation of p53
We know that p53 is very unstable, what really happens is that not only is p53 a transcriptional regulator, but it also regulates one of the genes called mdm2gene.
The mdm2 protein binds with p53 and forms p53 mdm2 complex. This complex degrades by ubiquitin-mediated, resulting in degraded p53 and the release of mdm2 protein. This can be a utilised for degradation of some more p53 protons.
Within a damaged DNA, there is already mdm2 available. p53 is also available; what really happens is that p53 gets phosphorylated. Once that has acquired, it prevents the formation of mdm2 complex. There is no p53 mdm2 complex and there is no digration; which initially means increased level of p53, this is the basic mechanism activation of p53 regulation and p53 proteins.
What happens if p53 is inactive?
Well the answer is simple DNA is damaged!
Under normal circumstances, p53 is normally available. Its role is to protect the cell by causing a cell cycle arrest. Whenever there is an inactivated p53; this results in no cycle arrest, which results in cell cycle progress with the damaged DNA. This causes lots of genomic instability and neoplastic transformation.
Figure 1 :(Ute M. Moll, and Oleksi Petrenko Mol Cancer Res 2003;1:1001-1008)
P53 can be inactivated by either mutation, or by heterozygous and homozygous loss of alleles.
Most human cancers are associated with p53 cancer mutation. Most common cancers, such as breast, colorectal, liver, lung, and ovarian cancer are most commonly implicated by mutation in p53 genes.
THE MDM2-P53 INTERACTION
In-text: (molecular cancer research, 2003)
molecular cancer research. (2003). The MDM2-p53 Interaction. online Available at: http://mcr.aacrjournals.org/content/1/14/1001#ref-list-1 Accessed 12 Jan. 2018.
MOLL, U. AND PETRENKO, O.
The MDM2-p53 Interaction
In-text: (Moll and Petrenko, 2003)
Moll, U. and Petrenko, O. (2003). The MDM2-p53 Interaction. online Molecular Cancer Research. Available at: http://mcr.aacrjournals.org/content/1/14/1001#ref-list-1 Accessed 12 Jan. 2018.