Apoptosis

Death receptor ligand Death receptor

Extrinsic Pathway

Decoy receptors (sequester ligand)

Intrinsic pathway
Ischaemia DNA damage

Cell m embra ne
Oxidative stress

Intermembrane space

Inner mitochondria membrane

Death inducing signalling complex (DISC)

TRAD D

FAD
p53 family
Permeability transition pore dependent apoptosis

cFLIP

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
Fas (CD95 / APO-1) TNF receptor 1
CypD ANT T VDAC AC Pore H2O H+ Bcl-2 members (anti apoptotic) MDM Pore P Po

Ligands
Fas Ligand TNF and Lymphotoxin alpha TWEAK TRAIL TRAIL

TRAMP
+ p53

TRAIL-R1 TRAIL-R2

DNA fragmentation

Inhibitor of Apoptosis protein family

BH3 only + p53 CIAP1 CIAP2 NAIP Survivin x-linked IAP Bruce Livin

Membrane Blebbing
Apoptotic cell

AIF (apoptosis inducing factor)

Endonulease G OMI / HtrA2 SMAC / DIABLO IAPS p53 + Cytochrome C

Phosphatidylserine is flipped to outer leaflet to provide signal for phagocytosis. In this way apoptotic cells are removed.

Rupture of outer mitochondrial membrane

APAF-1 (apoplosis protease activating factor 1)

Pro-caspase 9 (Initiator caspase)

Apoptosis plays a pivotal role in normal development, cancer, normal ageing and in neurological disorders such as Alzheimers disease and Parkinsons 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. 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

Apoptosome

Cleavage of actin, fodrin and gelsolin (cytoskeletal proteins) Cleavage of nuclear lamins

Caspase activation

I CAD

DNA Fragmentation

Caspase activated DNAase (CAD)

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Produced in collaboration with Claudie Hooper, Kings College London

Caspase activation mechanism:

Apoptosis antibodies from Abcam:

A) Procaspase activation
active caspase activation by cleavage cleavage sites

Product
active Caspase 3 active Caspase 3 Apoptosis inhibitor 5 Bax Bax Bax Bcl2 Bim Bim Cytochrome C p53 p63 p73 Survivin TRAIL

Clonality Applications
P P M P P M M P M P P P P P P 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

Host
Rb Rb Ms Rb Rb Rb Ms Rb Rb Rb Rb Rb Rb Rb Rb

Species Reactivity
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 Hu, Ms

Product code
ab13847 ab77973 ab56392 ab7977 ab10813 ab32503 ab692 ab15184 ab32158 ab90529 ab37318 ab63881 ab5399 ab8228 ab2435

Proteins

ab52314 ab52101 ab73697 ab85157 ab59854 ab73696 ab112387 ab43615 ab101717 ab101716 ab87202 ab9960

NH2

large subunit small subunit

COOH inactive procaspase

prodomain

active a ac cti ct tv tiv ve e caspase

B) Caspase cascade
one molecule of active caspase X

Featured antibodies cIAP2 (ab23423)

Clonality P Applications ICC/IF , WB Host Rb Species cross reactivity Hu

many molecules of active caspase Y

cleavage of cystolic proteins

Cytochrome C (ab13575)
Clonality Applications M ICC/IF , IHC-Fr, IHC-P , WB Host Ms Species cross reactivity Hu, Ms, Rat, Dm, Hrs, Pgn

Survivin (ab8228)
cleavage of vital cellular proteins

Clonality Applications P ICC/IF , IHC-P , WB

Host Rb

Species cross reactivity Hu

033_12_AH

even more molecules of active caspase Z

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