Resisting Cell Death W6

Question 1

P53 also induces apoptosis. How

Answer 1

Once activated, p53 binds to DNA and regulates the transcription of various target genes involved in cell cycle arrest, DNA repair, and apoptosis.

p53 activates pro-apoptotic proteins that lead to the mitochondrial pathway of apoptosis

proteins cause mitochondrial outer membrane permeabilization

Pro-apoptotic proteins disrupt the mitochondrial membrane, leading to the release of cytochrome c

Which binds to apaf-1 to form apoptosome which activated caspase-9 which activated caspase-3 and other executioner caspases leadin to cell death

Question 2

Normal P53 vs abnormal

Answer 2

• Normal p53 protein destroys cells that have irreparable damage to their DNA
• Abnormal p53 fails to stop cell division, damaged cells divide, cancer
develops

Question 3

What causes genomic instability?

Answer 3

• Loss or mutation of the DNA damage sensor protein p53
• Breakdown in one or more DNA repair mechanisms (e.g.
DNA mismatch repair, base excision repair)
• Mutagenic agents and viruses
• A combination of these factors

Question 4

Several strategies to resist cell death

Answer 4

1. Overexpression of Anti-Apoptotic Proteins (Bcl-2 Family)
2. Inactivation of Pro-Apoptotic Proteins
3. Mutations in the p53 Tumor Suppressor Gene
4. Activation of Survival Signaling Pathways (e.g., PI3K/Akt, MAPK)
5. Death Receptor Signaling Resistance
6. Overexpression of Inhibitors of Apoptosis Proteins (IAPs)
7. Alterations in Autophagy