Question

Background about the p53
i. What is p53?
ii. What are its functions
iii. How does post-translational modifications of protein such as phosphorylation, acetylation and ubiquitination affect p53 functions
iv. What is the role of MDM2 protein in regulating the biochemical stability of p53 protein
v. What is the composition/domains within p53 protein
vi. What are genes regulated by p53
vii. What it is essential to activate p53 in cancer
viii. What are most common mutations prevalent in p53 gene
ix. How does these mutations impact p53 protein and functions
x. Describe the structure and the role of DNA binding domain of p53
xi. Is there a relation between various cancers and type of mutations

Answer 1

1.P53 is a protein it is also called as the guardian of the cell cycle

it is the tumor suppressor gene presant on the 17th chromosome,

it is presant in all tissues ,

it is having short life span in normal cell.

2.It regulates cell cycle with interacting with different proteins

it repairs DNA

it activates apoptosis pathway

3. In normal cell mdm2 protein degrades p53 upon ubiquitination ,

if DNA damage occurs: p53 undergoes acetylation and phosphorylation ,they cannot bound to the mdm2 protein,which causes p53 levels to increase which inturn increases the protein p21 ,this p21 binds to the cdk-cyclin complex finally the cell cycle is halted.

4.p53 has short life cycle in normal cell the concentration of p53 is maintained by mdm2 protein,it is the protein that triggers the degradation of p53 by ubiquitin system.

5.It is having N-terminal transcription activation domain(TAD).

C-terminal for downregulation of DNA.

Activation domain and proline rich for apoptotic pathway .

Central DNA binding core domain.

Oligomerization domain.

6.p53 regulates many proteins mainly ,WAF-1 protein which upon translation produces a protein p21

7.DNA damage,virus infection,hypoxia,oncogenes---activates p53

8.p53 mainly associated with the missense mutations,with transitions and transversions.Cancers are associated with p53 mutations :breast ,ovarian, lung etc.,

9.DNA bindding domain binds to DNA motifs and is important for regulation of gene activation or repression.

10.Mutations(change in the DNA sequence) in the cell causes the production of abnormal cells ,mutations inactivate p53 gene ,inactivates DNA repair genes ,continous mutations leads to cancers.