Question

Please explain in detail the function of P53 including how it is activated in healthy cells and what it does when activated.

Answer 1

The answer to your query is as follows:

p53 which is also called as TP53 is a gene that encodes for a functional protein that controls the progression of the cell cycle. Its main function is to work as a tumor suppression gene thus plays a very important role in suppressing cancer in multicellular organisms.

It is made up of phosphoprotein which has 393 amino acids in it. It comprises four domains that:

• activates the transcription factors required in the process of transcription
• identifies specific DNA sequences
• cause the tetramerization of the protein
• Recognizes the damaged DNA

p53 is activated in the healthy cells when the DNA of the healthy cell is damaged and other stress signals have been produced in the cell.

p53 responds to this change by performing three major functions:

• Cell growth arrest
• DNA repair
• Apoptosis or cell death

The cell growth arrest does not lead to the progression of cell cycle. Thus, prevents the replication of the DNA that is damaged in the cell. p53 activates the transcription process of various proteins that might be involved in DNA repair mechanism.

Apoptosis is the last option for p53 after cell growth arrest and DNA repair and thus proliferation of the cells is stopped that contains the abnormal DNA.

The major regulator of p53 is Mdm2. It triggers the degradation of p53 gene by the ubiquitin system.

The target genes of p53 are as follows:

1. p21, Gadd45 for growth arrest

2. p53R2 for DNA repair

3. Bax, Apaf-1 for apoptosis

p53R2 is a transcriptional target gene that encodes for ribonucleotide reductase. This enzyme plays a very important role in replication of DNA and DNA repair mechanisms.

Another important action of p53 is the interaction of it with AP endonuclease and DNA polymerase enzymes which are directly involved in the process of the base excision repair.

The progression of the cell cycle into S phase of the interphase needs a enzyme Cdk2. This enzyme is inhibited by p21 and thus, it is p53 that checks and regulates the expression of p21 as a inhibitory protein to stop the cell cycle progression.

p53 can also activate the expression of Apaf1 and Bax genes. The Bax stimulates the release of cytochrome c from mitochondria. The release of the cytochrome c from the mitochondria leads to the apoptosis induction by binding it with Caspase 9.

Thus, p53 upon activation induces the expression of a large number of gene products. This causes a long cell-cycle arrest in G1 phase of the interphase causing apoptosis of the damaged cells in our body.

Hope it helps!