Question

What is protein that is related to p53 gene? How is this gene regulated? What is the protein that is formed? What is specific structure, what is function of this protein? How is this protein regulated post-translationally?

Answer 1

p53 gene and regulation: p53 gene is a tumour suppersor gene that encode p53 protein or tumour suppresor protein p53. The expression of this gene is regulated in relation to stress such as DNA damage, UV-light and ionizing radiations and by MDM2 protein.

The specific structure of p53: This protein is a phosphoprotein and made of 393 aminoacids. it consists of following domains

1. Transcription activation domain I (1-42): This domain is present at the N-terminus region of the p53 protein and is involved in the activation of transcription factor and regulate pro-apoptotic genes.

2. activation domain II (43-63): This domain is essential for apoptotic activity of the protein.

3. Proline rich domain (64-92) :  This domain is essential for apoptotic activity of the protein by MAP kinase and nuclear export.

4. DNA binding domain (102-292): To this domain p53 co-repressor LMO3 binds and regulates it activity.

5. Nuclear localization signal (316-325)

6. Tetramerization domain (307-355) : Tetramerization of p53 protein is essential for its activity.

7. C-terminal regulatory domain (356-393) : This a regulatory domain that regulates DNA binding domain of the p53 protein.

Function of the protein p53: This protein is DNA binding transcription factor which is known to regulate various genes involved in regulation of cell cylce, apoptosis and genome stability. If DNA of a cell is damaged by stress, p53 protein arrest the cell cycle at G1/S checkpoint or activate DNA repair enzymes. If DNA damage is irrepairable, it initiate apoptosis and cell death. It also regulate the expression of MDM2 gene. MDM2 protein inturn regulate the p53 protein.

Regulation of p53 protein post-translationally: In normal cells, p53 is in unphosphorylated state due to inactive ATM kinases. This unphosphorylated p53 protein binds to MDM2 protein and forms a complex. MDM2 is ubiquitin E3 ligase that promote ubiquitination and degradation of p53 proteins leading to decrease in the concentration of p53 protein. In DNA damaged cells, ATM kinase gets activated that post-translationally modify the p53 protein by phosphorylation. This phosphorylated p53 protein doesn't bind to MDM2 and the amount of p53 is increased in the cells, which regulate various genes involved in regulation of cell cylce, apoptosis and helps in maintaining genome stability.