Apoptosis case study

necorsis

cells spilling their contents over neighboring cells in response to cell death

components of apoptosis

1. cytoskeleton collapses

2. nuclear envelope disassembles

3. Nuclear dna breaks up intro fragments

in apoptosis the cell shrinks and collapses

without damaging neighboring cells

cell death and engulfment is triggered by

capases

caspase are

intracellular proteases active only during apoptosis

what are the two major classes of apaoptotic caspases

initiator and executioner

apoptotic process begins with the

initiator caspase

the initiator caspase triggers the assembly of

large protein platforms that bring multiple initiator caspase together into large complexes

dimer formation allows

protease activation

dimers cleave their partner at a specific site resulting in

complex stablization and therefore enzymatic function!

the initator caspase activates the

executioner caspase

executioner caspase catalyzes the wide scale

protein cleavage events that lead to cell death

the Int. caspase can be activated when

external signal proteins bind to cell surface death receptors

activation of FAS ligand on the surface of a cytotoxic lymphocyte engages the

FAS receptor

FAS recetpro engagement leards to

conformational changes and trimerization unducing more clustering at surface

activated FAS receptors recruit other molecules

FADD and initiaor caspaeses to form death inducing singaling complex

DISC

death inducing signaling complex

Once dimerized and activated in DISC the initator caspeases

cleave and activate executioner caspases

intiator caspase can turn into executioner caspase via

1. cleaving proasease

2. cleaves BID and COOH teminal

What are the key compoenents of DISC formation

1. FADD must be recruited

2. FADD complexes with caspase

initaor caspase activity can also trigger

BID and influence mitocondria function

mitochondria release cytochrome c which leads to the formation of the

apoptosome

Componenets of intrinsic apoptoic pathway

A. FAS and FADD initator caspase and executioner, BID and cytochrome c

the intrinsic pathway of apaoptosis depends on

mitochondiral proteins

mitocondria proteins released into the intermembrane space activates a

caspase cascade

cytochrome c (released from mitocondria) binds to

APAF1 causing oligomerization into an apoptosome

APAF1 proteins in the apoptosome recruit

initator caspases which activate downstream executioner caspase

inhibitory mechanisms help prevent the inappopriate activation of

apoptosis

c-FLIP

regulates the activation of initiator caspase at the DISC

flip resembles an

initiar caspase but has no protease activity

apopotic signal is blocked by

FLIP variations

intrinsic pathway is regulated by the

BCL2 protein family

BCL2 family subgroups

pro-apoptotic and anti-apoptoic

BAX and BAK BH3

proaptotic regulator proteins: enhance cytochrome c release

BCL2 and bclXL

reduce or block cytochrome c release