Apoptosis and cancer signaling pathways
The bcl-2 family consists ofpro- and anti-apoptotic
The bcl-2 family consists ofproteins involved in intrinsic
pro- and anti-apoptotic
mitochondrial cell death.
proteins involved in intrinsic
They regulate the release of
mitochondrial cell death.
apoptotic factors into the
They regulate the release ofcytoplasm, including
apoptotic factors into thecytochrome C and Apaf-1,cytoplasm, including
by mediating outer
cytochrome C and Apaf-1,membraneby mediating outerpermeabilization. This leadsmembrane
to activation of caspase-9
permeabilization. This leads
and the resulting caspaseto activation of caspase-9cascade.
and the resulting caspasecascade.

Caspase 3
Caspase 3

p53 signaling in apoptosis and gene transcription
p53 signaling in apoptosis and gene transcription

Cellular stress,
deathstimulus
Cellularstress,
death stimulus

Bcl-2 inihibitors
Bcl-2 inihibitors

Caspase 9
Caspase 9
Apaf-1
Apaf-1Apoptosis
Apoptosis

Bcl-2
Bcl-2
Cyt-c
Cyt-c

TNFα
TNFα
TNFR1 receptors
TNFR1 receptors

Death domain
Death domain

Death receptors (DRs)belong to the tumour
Death receptors (DRs)
necrosis factor (TNF) family
belong to the tumourof cytokines which induce
necrosis factor (TNF) family
apoptosis. These receptorsof cytokines which induce
can activate caspases within
apoptosis. These receptors
seconds, causing apoptosis.
can activate caspases within
seconds, causing apoptosis.
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Caspase 3
Caspase 3
Apoptosis
Apoptosis

Mitochondria
Mitochondria

Death receptor signaling in apoptosis
and genetranscription
Death
receptorsignaling in apoptosis
and gene transcription

Cyt-c
Cyt-c

TRADD
TRADD
TRAF-2
TRAF-2

FADD
FADD
Pro-caspase 8
Pro-caspase 8

BAX
BAX

BID
BID

DNA damage
DNA damage
Bax
Bax

IKK
IKK
Transcription
Transcription

Cyt-c
Cyt-c

Cell cycle arrest,
cellCell
growthcycleinhibition,
arrest,stresscellmetabolic
growth inhibition,
inhibition
metabolic stressinhibition

Apaf-1/Caspase 9
Apaf-1/Caspase 9

Apoptosis
Apoptosis

Apoptosis Pathway
Apoptosis Pathway

Mitochondria

NF-κB
NF-κB

Mitochondria

Inhibitors of apoptosis signaling in cellular apoptosis
Inhibitors of apoptosis signaling in cellular apoptosis

BidBidMitochondria
Inhibitors of apoptosis(IAPs) are a conserved
Inhibitors of apoptosis
group of proteins(IAPs) are a conserved
containing Baculovirus-IAP
group of proteins
repeats involved in thecontaining Baculovirus-IAP
regulation of apoptosis asrepeats involved in thewell as a number of otherregulation of apoptosis ascellular processes.
well as a number of othercellular processes.

Cyt-c
Cyt-c
Caspase 9Caspase 9

Gene regulation
Gene regulationMitochondria

Bcl-2
Bcl-2

p53 is a criticaltumor-suppressing
p53 is a criticaltranscription factor whichtumor-suppressing
responds to cellular stresstranscription factor whichby triggering cell cycle arrest
responds to cellular stressand apoptosis throughby triggering cell cycle arrest
transcriptional regulation.
and apoptosis throughtranscriptional regulation.

Cellular stress
Cellular stress

p53
p53

Caspase 8Caspase 8
Smac
Smac

DR4/5
DR4/5

Bcl-2 signaling in cellular apoptosis
Bcl-2 signaling in cellular apoptosis

TRAIL
TRAIL

Smac-mimetic(SH122)Smac-mimetic(SH122)XIAP
cIAP-1XIAP
cIAP-1PARP cleavage
Caspase 3 PARP cleavage
Caspase 3

NF-κB Pathway
NF-κB Pathway
RelA
RelA

IκBα
IκBα

IκBα
IκBα
Degradation
Degradation

NF-κB
NF-κB
Apoptosis
Apoptosis