APOPTOSIS
“Cell Death”
By Brian Abadie, Emily Anderson, andJohn Ramsey
Characteristics of Apoptosis





Shrinks
Blebbing
Nucleus breaks
down, breaks into
small membrane
wrapped
fragments
Phagocyte signals
Apoptosis Video
Importance of Apoptosis




Maturing
organisms
Virus
Immune System
DNA damage
What is a Caspase?



Single chain of pro-enzymes
Contains an N-terminal domain, a small subunit and
a large subunit (similar to a ribosome)
Apoptotic stimulus Activation Substrate
Cleavage Enzyme
3 Types of Caspases


Inflammatory Caspases: -1, -4, and -5
Initiator Caspases: -2, -8, -9, and -10
 Long
N-terminal domain
 Interact with effector caspases

Effector Caspases: -3, -6, and -7
 Little
to no N-terminal domain
 Initiate cell death
Two Caspase Pathways
Extrinsic Pathway

Death Ligand

Death Receptors

Caspases

Cell Death
Two Caspase Pathways
Intrinsic Pathway

Mitochondria

Cytochrome C

Apoptosome Complex

Caspases

Cell Death
Two Caspase Pathways
Cancer and Apoptosis

http://www.youtube.com/watch?v=qjjHKDn12qI

Evasion of apoptosis can lead to cancer
Treatment Options






Activate apoptosis in cancer cells, problem solved.
Finding useful mechanisms
Needs to be selective
Pathways (trail)
IAPs
Seaweed?
IAPs
Inhibitor of Apoptosis Proteins
Neutralize them or prevent their production
 Inhibit one part in the cascade = failure to
apoptose
 Smac mimetics
 Bcl proteins
 Elevated Bcl
Confers resistance to
chemotherapy

Gene Expression
Down regulation of XIAP
Most potent endogenous IAP
 Using Adenovirus vector
 ShRNA achieves delivery
And long term inhibition
