Cell death Flashcards
what triggers the steps of apoptosis?
caspases. once activated they cleave proteins within the cell leading to death
what is the main function of initiator caspases?
they begin the apoptotic process. adaptor proteins dimerize initiators which activate protease, cleaves each other, and activates complex.
Main function is to activate executioner caspases. one initiator can activate many (thousands) executioners
what is the main function of executioner caspases?
initiator caspase cleaves executioners and they are activated. They function to cleave thousands of other proteins and actively kill the cell in an irreversible cascade
example of what executioner caspases will do once activated. (CAD)
executioner caspases will free endonuclease (CAD) from it’s inhibitor iCAD. Once active, CAD cuts chromosomal DNA resulting in DNA fragmentation
two ways to activate caspase cascade
intrinsic: mitochondrial pathway. activation as result of DNA damage or developmental signals. depends on cytochrome C which binds Apaf1, forms wheel like oligomer, recruits caspase 9, activates downstream executioners
extrinsic: activation outside cell. result of activation of death receptors (Fas/DR2). extracellular signal molecules bind death receptors, forming homotrimers, activating adaptor proteins which bind caspase 8 to make death-inducing signaling complex
Which pathway involves Fas?
extrinsic. Fas ligand binds to Fas death receptors and forms a homotrimer that activate the caspase cascade
how can apoptosis be prevented?
anti-apoptotic Bcl2 proteins, inactivated pro-apoptotic proteins, and inactivated anti-inhibitors of apoptosis proteins (anti-IAPs)
What is Bcl2?
Bcl2 regulates the intrinsic pathway. it’s a big family of proteins, some are pro-apoptotic and some are anti-apoptotic. Bak and Bak, when triggered, come together in mitochondria membrane to release cytochrome c. Bcl2 or BclX will interact with other Bcl2 proteins in cytosol and block from releasing cytochrome c.
what are IAPs?
Inhibitors of apoptotic proteins. They bind to activated caspases and inhibit them if apoptosis is not needed
what are anti-IAPs?
they bind to IAPs and stop them from working, therefore allowing caspases to work and causing apoptosis
what are survival factors?
continuous signals required by most cells to avoid apoptosis. survival factors bind to cell surface receptors and activate pathways that block apoptosis.
What diseases can result from too much or too little apoptosis?
too much: neurodegenerative diseases, cancers, AIDs
too little: Leukemia, autoimmune diseases, other cancers
