Apoptotic cell death

Question 1

what is p14/ARF? what is its function?

Answer 1

p14 is a tumour suppressor protein

p14 is a part of the ARF/Mdm2/p53 signalling pathway–>
p14 inhibits Mdm2; Mdm2 inhibits p53.
Therefore, increased level of p14 increase the level of p53 by Mdm2 inhibition

NOTE: p14 is made from an alternative reading frame for the gene of p16 but has no homology with this family of CKIs;

Question 2

What is Mdm2? what is its function?

Answer 2

• It’s also known as ‘E3 ubiquitin ligase Mdm2’
• it binds to and ubiquitinates p53, facilitating it for degradation
• there is a negative feedback loop between Mdm2 and p53–> high levels of p53 induce transcription of Mdm2 & Mdm2 then induces the degradation of p53

Question 3

what is p53? what is its function?

Answer 3

p53 is a transcription factor;

its activation domain are involved in regulation of several pro-apoptotic genes