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

Intrinsic Pathway

Mitochondria

Cytochrome C

Apoptosome

Complex

Caspases

Cell Death

Two Caspase Pathways

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 ProteinsNeutralize them or prevent their

production Inhibit one part in the cascade =

failure to apoptose Smac mimetics Bcl proteins Elevated BclConfers resistance to chemotherapy

Gene Expression

Down regulation of XIAPMost potent endogenous IAP Using Adenovirus vector ShRNA achieves deliveryAnd long term inhibition