033_12_AH Apoptosis Pathway Card Side01:Layout 1 28/02/2012 11:31 Page 1
Apoptosis
Extrinsic Pathway
Death receptor
ligand
Death receptor
Decoy receptors
(sequester ligand)
Intrinsic pathway
Ischaemia
Cell m
embra
ne
DNA damage
Oxidative stress
Inner mitochondria
membrane
Intermembrane
space
Death inducing
signalling
complex (DISC)
TRAD
D
FAD
cFLIP
p53 family
Permeability transition
pore dependent apoptosis
Outer mitochondria
membrane
Permeability transition pore
independent apoptosis
(Bcl-2 family)
• p53 isoforms
• p63 isoforms
• p73 isoforms
• N dominant
negatives
pro-caspase 8
(Initiator caspase)
Death Receptors
MDM
Pore
P
Po
CypD
ANT
T
p53
+
VDAC
AC
Pore
H2O
Ligands
Fas (CD95 / APO-1)
Fas Ligand
TNF receptor 1
TNF and Lymphotoxin alpha
TRAMP
TWEAK
TRAIL-R1
TRAIL
TRAIL-R2
TRAIL
Bcl-2 members
(anti apoptotic)
H+
Inhibitor of
Apoptosis
protein family
DNA
fragmentation
BH3 only
• CIAP1
• CIAP2
• NAIP
• Survivin
• x-linked IAP
• Bruce
• Livin
+
AIF (apoptosis
inducing factor)
Membrane Blebbing
p53
Apoptotic cell
Phosphatidylserine is flipped to outer leaflet to provide signal for
phagocytosis. In this way apoptotic cells are removed.
Endonulease G
OMI / HtrA2
Apoptosis plays a pivotal role in normal development, cancer,
normal ageing and in neurological disorders such as Alzheimer’s
disease and Parkinson’s disease. Apoptosis is induced via two main
routes involving either the mitochondria (the intrinsic pathway) or
the activation of death receptors (the extrinsic pathway), however
both pathways converge to induce the activation of caspases.
Apoptotic cells are ingested by phagocytes preventing inflammation
and tissue damage that might ensue upon cell lysis. The presence
of the phospholipid phosphatidylserine on the outer leaflet of the
plasma membrane acts as a signal for removal of apoptotic cells.
SMAC /
DIABLO
Rupture of outer
mitochondrial membrane
IAPS
p53
+
Cytochrome C
+
APAF-1 (apoplosis
protease activating
factor 1)
+
Pro-caspase 9
(Initiator caspase)
Apoptosome
Cleavage of actin, fodrin
and gelsolin (cytoskeletal
proteins)
Caspase activation
I CAD
Cleavage of
nuclear lamins
DNA Fragmentation
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Produced in collaboration with Claudie Hooper, King’s College London
Caspase activated
DNAase (CAD)
ANT: Adenine nucleotide transocator
VDAC: Voltage dependent anion channel
CypD: Cyclophilin D
MDM: Multi domain members
TRADD: TNFR associated death domain
FAD: fas associated death domain
cFLIP: Cellular FLICE like inhibitory protein
033_12_AH Apoptosis Pathway Card Side02:A4 05/03/2012 08:43 Page 1
Caspase activation mechanism:
Apoptosis antibodies from Abcam:
A) Procaspase activation
Product
­
active
caspase
NH2
activation
by cleavage
large
subunit
small
subunit
cleavage sites
COOH
inactive
procaspase
prodomain
active
a
ac
cti
ct
tv
tiv
ve
e
caspase
B) Caspase cascade
Clonality Applications
active Caspase 3
P
active Caspase 3
Apoptosis inhibitor 5
Bax
Bax
Bax
Bcl2
Bim
Bim
Cytochrome C
p53
p63
p73
Survivin
TRAIL
P
M
P
P
M
M
P
M
P
P
P
P
P
P
Host
Flow Cyt, ICC, ICC/IF, IHC (PFA fixed), IHC-FoFr,
IHC-Fr, IHC-P, WB
WB
IHC-P, WB
IHC-Fr, IHC-P, IP, WB
ICC/IF, IHC-P, IP, WB
IHC-P, IP, Sandwich ELISA, WB
Flow Cyt, IHC-Fr, IHC-P, IP, WB
IHC-P, WB
ICC, IHC-P, IP, WB
ICC/IF, WB
WB
IHC-P, WB
ICC/IF, WB
ICC/IF, IHC-P, WB
ICC/IF, IHC-Fr, IHC-P, IP, Measuring secreted
proteins from cells, WB
Rb
Species Reactivity
Rb
Ms
Rb
Rb
Rb
Ms
Rb
Rb
Rb
Rb
Rb
Rb
Rb
Hu, Ms, Rat, Dm,
InMtj, RMk, Xl, Zfsh
Hu
Hu
Hu, Ms, Rat
Hu, Ms
Hu, Ms, Rat
Hu, Ms
Hu
Hu
Hu, Ms, Rat
Hu
Hu, Ms, Rat
Hu
Hu
Rb
Hu, Ms
Product code
ab13847
Proteins
­
ab52314
ab77973
ab56392
ab7977
ab10813
ab32503
ab692
ab15184
ab32158
ab90529
ab37318
ab63881
ab5399
ab8228
ab52101
ab73697
ab85157
ab59854
ab73696
ab112387
ab43615
ab101717
ab101716
ab87202
ab2435
ab9960
Featured antibodies
­
one molecule of
active caspase X
cIAP2 (ab23423)
Clonality
P
many molecules of active caspase Y
cleavage of
cystolic
proteins
Applications
ICC/IF, WB
Host
Rb
Species cross reactivity
Hu
Host
Ms
Species cross reactivity
Hu, Ms, Rat, Dm, Hrs, Pgn
Host
Rb
Species cross reactivity
Hu
Cytochrome C (ab13575)
Clonality Applications
M
ICC/IF, IHC-Fr, IHC-P, WB
Clonality Applications
P
ICC/IF, IHC-P, WB
033_12_AH
Survivin (ab8228)
cleavage of
vital cellular
proteins
even more molecules of active caspase Z
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Copyright © 2012 Abcam, All Rights Reserved.