Cell Death and Damage

Answer 1

IF BCL-2 FAMILY PROTEINS REGULATE CYTOCHROME C RELEASE FROM mitochondria, WHAT regulates BCL-2 PROTEINS?
• TP53 mechanism
o DNA damage triggers activation of TP53 gene expression
o The release of cytochrome C can also be induced through intracellular stress. This increases the transcription of Bax that is one of the target genes of p53 when responding to the cell stress.
o This increases the number of Bax complexes in the mitochondrial membrane creating new pores in the mitochondrial membrane for cytochrome C (existing Bax pores occupied by Bcl-2 are not affected).
o This allows release of cytochrome C which leads to death
• Growth factors- phosphorylation mechanism
o Survival signals (GF) like AKT/PKB phosphorylate Bad
o Bad can no longer displace BCL-2, pore isn’t open
o Cytochrome C isn’t released
o Allowing cell to survive

• DNA damage-mediated apoptosis. If DNA is damaged due to radiation or chemo therapeutic agents, p53 (tumour suppressor gene product) accumulates. This arrests the cell cycle enabling the cell to repair the damage. If repair process fails, p53 triggers apoptosis.

Two types of apoptosis
• Intrinsic
o DNA damage – p53-dependent pathway

Question 2

IF BCL-2 FAMILY PROTEINS REGULATE CYTOCHROME C RELEASE FROM mitochondria. WHAT regulates BCL-2 PROTEINS.

What is the TP53 mechanism?

Answer 2

• TP53 mechanism
o DNA damage triggers activation of TP53 gene expression
o The release of cytochrome C can also be induced through intracellular stress. This increases the transcription of Bax that is one of the target genes of p53 when responding to the cell stress.
o This increases the number of Bax complexes in the mitochondrial membrane creating new pores in the mitochondrial membrane for cytochrome C (existing Bax pores occupied by Bcl-2 are not affected).
o This allows release of cytochrome C which leads to death

Question 3

What is the phosphorlyation mechanism?

Answer 3

Growth factors- phosphorylation mechanism
o Survival signals (GF) like AKT/PKB phosphorylate Bad
o Bad can no longer displace BCL-2, pore isn’t open
o Cytochrome C isn’t released
o Allowing cell to survive

Question 4

What happens if DNA is damaged?

Answer 4

DNA damage-mediated apoptosis. If DNA is damaged due to radiation or chemo therapeutic agents, p53 (tumour suppressor gene product) accumulates. This arrests the cell cycle enabling the cell to repair the damage. If repair process fails, p53 triggers apoptosis.

Question 5

What are the 2 types of apoptosis?

Answer 5

Two types of apoptosis
• Intrinsic
o DNA damage – p53-dependent pathway