NEOPLASIA 4: p53 gene: The Guardian of the genome. functions, regulation and inactivation

This Short tutorial explains p53 Gene.
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p53 GENE
This is a tumor suppressor gene ( its activity stops the formation of tumors)
Located on 17p13, first discovered in 1979
The p53 protein is the product of p53 gene
P-protein
53- weight of the protein, 53 kDa
Located in almost all normal tissues
Unstable and degrades very quickly
Is one of the most commonly mutated gene in cancer
Function
Regulation of Cell cycle
DNA repair
Apoptosis
Prevents neoplastic transformation either by cell cycle arrest or by triggering apoptosis.
In cases of DNA damage, there is triggering of expression of p53 gene whcich increases the production of p53 proteins. These preoteins Prevent Cell from entering S phase of cell cycle
and Allows time for the DNA repair to take place. also p53 induces DNA repair genes. If the DNA is repaired,the p53 degrades and the cell cycle continues. if the DNA is not repaired, the p53 induces permanent arrest in the cell or activates pro apoptotic proteins bax and bad thereby promoting apoptosis. By these mechanisms, it is understood that the p53 conserves the stability of the cell and thus aptly called as ' THE GAURDIAN OF THE GENOME"
How p53 causes cell cycl arrest?
P53 is the transcriptional regulator of one of the genes named WAF 1
Resulting in increased WAF proteins named as p 21
P21 blocks CDK4/CyclinD complex ….. Cell cycle is halted in G1 stage resulting in cell cycle arrest.
Regulation of p53 protein: by formation of p53 and mdme protein complex which is degraded by ubiquitin mediated pathway.
What happens when p53 is inactivated?
There will be no cell cycle arrest in cases of damaged DNA and the cell cycle progresses with damaged DNa which results in genomic instability and the neoplastic transformation.
How p53 is inactivated??
Mutations
Heterozygous and homozygous loss of alleles
What are the cancers associated with p53 mutations??
Most human cancers!
MC breast, colorectal, liver, lung, and ovarian cancers.
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Please watch: "WARBURG EFFECT: Hallmark of CANCER. What, Why & How?"
• NEOPLASIA 6: WARBURG E...
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P53 is guardian of the genome / old man of the genome/ police man of the genome / care taker / gate keeper of the genome .
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Thank you so much for making the concept clear and easy to understand

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Very good job at outlining this topic - this is a perfect and easy to understand introduction to p53, so now I can go and delve deeper! I do wish you had explained a bit more as to what causes p53 inactivation and how, but all in all great video!

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wonderful illustration of role of p53 gene

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I m actually dealing a while with p53 but the Video is Great

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[@svartmetall48]

I realise this is a very brief look at p53, so I'll leave out some of the simplifications, but I would say one thing needs to be corrected regarding the molecular weight. p53 was named because it ran on an SDS-PAGE gel at 53 kDa, not because its molecular weight is 53 kDa. Due to the fact that p53 is quite proline rich it is a more rigid structure with annoying "kinks" in it, and thus it migrates differently on SDS-PAGE. As I am sure you know, proteins don't necessarily migrate at their actual mass (and there are a plethora of reasons for this). p53 is around 44 kDa.

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@johnny torres Probably a good thing if you attend KI. I should know, I taught some of the undergraduate labs that med students took! ;)

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Nicely illustrated about p53 gene regulation in tumor suppression

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Good stuff and explanation! However I wish p53 videos also mention that it's part of the BAX/BAK pathway and Bcl2 as that can be a point of confusion.

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