文档介绍：APOPTOSIS: control
Receptor pathway (physiological):
Death receptors:
(FAS, TNF-R, etc)
FAS ligand
TNF
Death
domain
Cysteine Asparatic acid specific protease
Aps-Xxx
天冬氨酸特异性的半胱氨酸蛋白水解酶
Caspases Trigger a Proteolysis Cascade
Cleaves inhibitors of DNase
DNA fragmentation
APOPTOSIS: Role in Disease
Cancer
Apoptosis eliminates damaged cells
(damage => mutations => cancer )
Tumor suppressor p53 controls senescence
and apoptosis responses to damage
Most cancer cells are defective in apoptotic response
(damaged, mutant cells survive)
High levels of anti-apoptotic proteins
or
Low levels of pro-apoptotic proteins
===> CANCER
TRAIL: 一种细胞凋亡诱导蛋白质
TRAIL: 肿瘤坏死因子相关的凋亡诱导配体
TRAIL肿瘤选择性: 不同TRAIL受体表达的结果
死亡受体(DR4，DR5):
介导细胞凋亡信号
诱骗受体 (DcR1，DcR2) :
不传导细胞凋亡信号
DcRs 与 DRs 竞争结合TRAIL，赋予正常组织TRAIL抗性
TRAIL变体具有更好的细胞凋亡活性
Adaptor proteins bring many copies of initiator procaspase
together
Initiator caspase has low activity, but when they form
aggregates, they can cross-activate each other.
Aggregation causes conformational changes
Apoptosis Is Activated by Binding to Adaptor Proteins to Form Aggregates
F
a
s
F
a
s
L
F
A
D
D
C
a
s
p
a
s
e
8
A
P
O
P
T
O
S
I
S
Activation of Apoptosis from Outside the Cell
Death receptors
Killer lymphocytes produce Fas
ligand to bind to Fas protein (death
receptor) on target cells
Adaptor proteins aggregate
caspase 8, which cross-activate
Some damaged cells produce both Fas ligand and Fas protein for self-destruction
Extrinsic pathway
APOPTOSIS: control
Intrinsic pathway (damage):
Mitochondria
Cytochrome c release
Pro-caspase 9 cleavage
Pro-execution caspase (3) cleavage
Caspase (3) cleavage of cellular proteins,
nuclease activation,
etc.
Death
BAX
BAK
BOK
BCL-Xs
BAD
BID
B IK
BIM
NIP3
BNIP3
BCL-2
BCL-XL
BCL-W
MCL1
BFL1
DIVA
NR-13
Several
viral
proteins
Activation of Apoptosis from Inside the Cell
Intrinsic pathw