FOM 6.4.2 Flashcards
What is the difference between apoptosis and necrosis?
Apoptosis - controlled, single cell, no inflammation
Necrosis - uncontrolled and inflammation
Signaling through the death receptor immediately leads to what events?
Recruitment of scaffolding proteins
Scaffolding proteins recruit caspase 8
Increased concentration of caspase 8 induces self cleavage?
How does regulation affect caspase proteins?
Caspases are broken down into two categories: effector and initiator caspases. Initiator are recruited to the receptor, tightly regulated and upon activation cleave other caspase proteins. Effector caspases are what are cleaved by initiators, and upon cleavage they go and act upon a variety of substrates.
These are synthesized as zymogens
What is the active site of a caspase and what is its typical target?
Caspases contain a catalytic cysteine residue, and this likes to cleave proteins at aspartate residues.
How can caspases be inhibited?
Inhibitors of apoptosis (IAP) proteins can suppress apoptosis by binding and inhibiting initiator and effector caspases. These bind and alter the structure of the active site
Caspase activation leading to increase kinase activity can have what effect?
It can lead to hyper-activation of signaling pathways and increasing Ca2+ concentration within the cell
Caspase activation leading to interactions with intermediate filaments can have what effect?
Activated caspases can interact with intermediate filaments and degrade them; leading to loss of structural integrity of the cell
Caspase activation leading to interactions with PARP can have what effect?
Caspases can cleave PARP leading to no DNA repair within the cell.
How can caspase activation lead to DNA degradation?
Activated caspases cleave ICAD which is bound to caspase activated DNase (CAD). Upon cleavage, CAD is released from ICAD and it can go out and degrade chromosones
How can caspase activation affect the nuclear envelope?
Caspase activation can lead to degradation of lamins which leads to the breakdown of the nuclear envelope
Caspase activation has what effect on phosphatidyl serine
When normal the flippase enzyme is working against scramblase to put phosphatidyl inside the cell. Upon activation of caspases, flippase is inhibited and scramblase is free to put phosphatidyl serine on the outside of the cell.
The BCL-2 family has what two classes of proteins?
Anti-apoptotic and pro-apoptotic proteins
Activation of apoptosis has what effect on the BCL-2 family?
Activation of apoptosis leads to BH3 sensitizer which disrupts anti-death and activators interactions. The activators can then interact with pro-death proteins and promote mitochondrial permeability. Leading to pore formation in the mitochondrial membrane
Mitochondria outer membrane permeability increase can have what effect on the rest of the cell?
Loss of proton gradient, loss of ATP formation, increased reactive oxygen species formation, and finally leakage of cytochrome c to the cytosol.
Leakage of cytochrome c out of the mitochondria can have what effect?
FORMATION OF THE APOPTOSOME!!! The freaking death star of all cellular degradation. This acts as a super initiator and leads to the activation a ton of caspases
