Apoptosis

Phagocytosis Contains SH3 domain

Mitochondria The Bcl-2 Family Ligand (TNF)
(trimer, contact
TNF-family death receptors
Engulfing
which allows residues in red)
Phosphatidyl serine (PS) phagocyte interaction with C
TNF FasL TRAIL TRAIL
Pro-apoptotic Bcl-2 family members promote, N
normally on the inner leaflet signaling pathways -
and anti-apoptotic Bcl-2 family members block
Anti-apoptotic
of the plasma membrane PS receptor regulation of
Bax mitochondrial cytochrome c release Bcl-2, Bcl-x L, BH4 BH3 BHI BH2 TM
‘flips’ to the outer leaflet (CDI4?) DOCK I80 cytoskeleton and TNF receptor (TNFR)
Mcl-I TNFR Fas TRAIL-RI TRAIL-R2
(CED5 homolog) cell motility ? (monomer, cysteines in yellow,
Bcl-w, A-I BH4 BH3 BHI BH2 TM contact residues in red)
*CD36 Cytochrome c
TSP, macrophage *Adhesion molecules
Croquemort
which bind TSP
secreted (drosophila)
and signal via
Pro-apoptotic
glycoprotein Thrombospondin
which provides a tyrosine kinases Apoptosome Bax, Bak, BH4 BH3 BHI BH2 TM Death
(TSP) moiety *αvB3 TRAF- I
‘bridge’ between Mtd/Bok domain FADD FADD
Apaf-I Caspase-9 Caspases- TRAF-2
the macrophage Ion flux tetramer 3,6,7 TRADD
PS? ABC Transporter c-IAP
and an apoptotic cell Bcl-x S BH4 BH3 TM Unknown adaptor
ATP (CED7 homolog)
Inhibits TNF- Recruits and permits Recruits and permits ? recruits and permits
CDI4 role in phagocytosis Procaspase-9 induced apoptosis caspase-8 transactivation caspase-8 transactivation caspase-8 transactivation
Exposure of sugar Plasma membrane-bound unclear Bcl-x L blocks? Bik, Hrk, BH3 TM
residues on cell-surface glycoprotein which binds Bim, Blk Death effector domain
carbohydrates lipid molecules Death domain
Bad, Bid BH3
Lectins TNF Tumor necrosis factor
recognize and interact TRAIL TNF-related apoptosis-inducing ligand
Apoptotic with sugars TRADD TNF-receptor-associated death domain
cell Active FADD Fas-associated death domain
Apoptosis caspase-8 TRAF TNFR-associated factor
tetramer IAP Inhibitor of apoptosis protein

DNA fragmentation
Stress signals DNA damage
I80 bp oligo-
nucleosomal
Execution Nuclear
signal
fragments T- cell receptor activation

Inactive
complex IKKI/IKK2
Internucleosomal IKKI/IKK2 IκB
DNA cleavage p53
NF -κB
Calcineurin JNK/SAPK
P
Phosphorylation IκB
Transcriptional
Active and dissociation NF -κB

Burial
regulation
Active caspase-3 NF-AT Active Fos/Jun
CAD/ e.g.Bax
nuclease
DFF40/
CPAN
iC AD/
DFF45 Initiation heterodimers

EGR-3 NF-AT NF -κB NF -κB AP-I

Death
EGR-3
FasL transcription
Substrate FAK
IC AD-L
Focal adhesion kinase
Inhibitor of caspase-activated DNAse
PAK-2 p2I-associated kinase
cleavage PARP
PKC
Poly-ADP-ribose polymerase
Protein kinase C
Granzyme B Survival IGF-I IL-3
Gelsolin MEKK- I SCF
Caspases Cytotoxic T cell signals IL-3R
FAK
PAK-2 Gel-DQTD 352 G-solin ME-DTVD 874 G-KK- I IGF-IR
Mediate membrane and IGF-IR Insulin-like growth Kit
morphological changes Granzyme B Perforin factor I receptor (SCF-R )
PA-EVD 212G-K-2 F-VSWD 704 S-AK Loss of cellular adhesion
F-DQTD 772 S-AK (GrB ) IL-3R Interleukin-3 receptor
SCF-R Stem cell factor Ceramide PI 3-kinase wortmannin
Non-classical receptor- receptor
IC AD-L (-S) mediated entry Gr B+ Target cell
DNA-PK AKT (PKB) FREE
DNA fragmentation
IC -DEPD 117 -AD-L Phosphorylation and PERSONALIZED
PARP
IC -DAVD224-AD-S DNA-DEVD 2712 N-PK Mechanism of perforin inactivation
Akt Antibody Detective
3 6 7 8 10 9 2 I 4 5 rab5+ entry unknown of Bad *Required for
Disable DNA repair Gr B+ ?
Bad
survival-promoting activity
Service
PA-DEVD 213 G-RP mechanisms Sequestration
PKC- δ Executioner caspases Initiator caspases Inflammatory caspases
Activated of Bad
*SerI36 P *SerI36 P
caspase tetramer
Death effector domain Prodomain rab4+ Bad Bad
Other target substrates: Bcl-x L 14-3-3
Retinoblastoma PKC- DMQD 330 N -δ Gr B+ SerII2 SerII2
Caspase recruitment domain Protease subunits
pro-IL-I β (caspase-I) Executioner
Disruption of cell-cycle rab5– Perforin caspase
laminsA/C (caspase-6)
control Adaptors Initiator Executioner caspase rab4– Dissociation
Retino-DEAD 886 G-blastoma fodrin, Mdm2, UI -70 kDa, actin (caspase-3) P
caspase lgpI20 – of Bad/Bcl-2 and *SerI36
Cathepsin D – Gr B+ Bad/Bcl-xL Bad
SerII2
Cytochrome c– heterodimers
M-6-P-R –
Helen M. Beere and Douglas R. Green Bcl-2 Neutralization of
Cytosolic Bcl-x L
La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA Transactivation Active caspase pro-apoptotic effects
tetramer (2 heterodimers)
granzyme B Death Bax
With thanks to Joshua Goldstein, Carl Ware, Michael Pinkoski, Shailaja Kasibhatla and Nigel Waterhouse of Bax
Copyright © 1998 Elsevier Science Ltd. All rights reserved. Based on an original design by Sheila Betts. www.abdserotec.com/ADS

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LIT.APOP.2010.1