Apoptsis Flashcards
what happens during apoptosis?
cytoskeleton collapses, nuclear envelope disassembles
nuclear DNA breaks into fragments
phosphatidylserine on cell surface causes phagocytosis
how can apoptosis be triggered?
extrinsic pathway- death receptor activation
intrinsic pathway- internal trigger
what does an active caspase do?
invoke apoptosis, digest certain proteins
how does a caspase get activated?
apoptosis signals clusters inactive caspases. inactive procaspases get their prodomains cleaved. this cleaves executioner caspases then cleave other substrates
how does DNA get cleaved?
executioner caspase cleaves inhibitory CAD and then the now active CAD cleaved DNA
explain extrinsic pathway
receptors binds with fas ligand thats on a killer lymphocyte. FADD adaptor protein’s death doman binds to receptors death domain. caspase 8’s death effector domain binds to FADD’s death effector domain. receptor+FADD+caspase=DISC. procaspases cluster and cleave each other, activating the caspases
explain intrinsic pathway
cytochrome c released from intermembrane space in mitochondria and binds to Apaf 1. CARD domain on Apaf 1 bind on other Apaf 1s and form a wheel looking shit called apoptosome. procaspase 9’s CARD domain binds to apoptosome’s and clusters to cleave each other
how is a procaspase different from a caspase?
a procaspase turns into a caspase when they cluster and cleave each other
what regulates release of cytochrome c in the intrinsic pathway?
Bcl-2 family
what are the 3 categories of the Bcl-2 family?
anti-apoptotic Bcl-2
pro-apoptotic effector
pro-apoptotic BH3-only
what are Bcl-2 homology domains?
areas where proteins look similar
anti-apoptotic Bcl-2 has what BHs?
all 4, BH4/3/1/2
pro-apoptotic effector has what BHs?
BH3/1/2
pro-apoptotic BH3-only protein has what BHs?
BH3
what does pro-apoptotic effector do?
apoptotic stimulus causes them to aggregate and cluster to releases cytochrome c
what does the anti-apoptotic Bcl-2 do?
inhibit pro-apoptotic effector to stop release of cytochrome c
what does pro-apoptotic BH3-only do?
inhibits anti-apoptotic Bcl-2 thats inhibits pro-apoptotic effector to stop release of cytochrome c (ALL IN ALL MOVES FORWARD WITH APOPTOSIS) and helps aggregate pro-apoptotic effector has what too
what is IAP?
bind to activated caspase to block them when they are spontaneously activated, inhibitors of apoptosis
what is anti-IAP?
gets released with cytochrome c to inhibit IAP to allow for apoptosis
how do you regulate apoptosis?
- increased production of anti-apopototic bcl2 family protein
- inactivation of pro-apoptotic BH3-only protein
- inactivation of anti-IAPs
how does increased production of anti-apopototic bcl2 family protein help regulate apoptosis?
survival factor and receptor activates transcription regulator to produce Bcl2 protein to block apoptosis
how does inactivation of pro-apoptotic BH3-only protein block apoptosis?
survival factor binds to receptor which activates Akt kinase to take away Bcl2 inhibitor (Bad, BH3 only) through phosphorylation
how does inactivation of anti-IAPs regulate apoptosis?
survival factor and receptor activates map kinase to phosphorylate Hid to inactive it. active Hid will inhibit IAPs.
