L10

Question 1

Ways to target anti-apoptotic Bcl2?

Answer 1

1. Target w/antisense oligonucleotides (18 nts)
2. BH3 mimetics
3. Smac mimetics

Question 2

8 alternate forms of cell death

Answer 2

1. Regulated necrosis or necroptosis
2. Autophagic cell death
3. Mitotic catastrophe
4. Lysosomal cell death
5. Entosis
6. Anoikis
7. Methuosis
8. Ferroptosis
9. Recovery from death: anastasis

Question 3

Describe Regulated Necrosis (Necroptosis)

Answer 3

• necrosis can occur in a regulated manner in physiological and pathological settings
• involves activity of RIP1 and/or RIP3 kinase (RIPK = Receptor (TNFRI)-­interacting serine/threonine kinase)
• activated in response to caspase inhibition
• may involve death receptors

Question 4

How can necrosis/necroptosis be inhibited?

Answer 4

• RIP1K mediated necroptosis can be inhibited by NECROSTATINS (= family of compounds that can block regulated necrotic cell death; some act by blocking RIPK1 activity (others unknown)

Question 5

What are ZVAD-fk

Answer 5

permanant pan-caspase inhibitor that irreversibly binds to catalytic site of caspase proteases and can inhibit induction of apoptosis

Question 6

What is anoikis?

Answer 6

• “homelessness”

- Apoptotic response of adherent cells due to absence of cell-­to-­matrix interactions