高级细胞生物学.pptx

高级细胞生物学.pptxCaspase-mediated programmed cell death pathways as potential therapeutic targets in cancer
PCD : 程序性细胞死亡
Atgs: 自噬相关基因
IAPs: 细胞凋亡抑制剂
TNF : 肿瘤坏死因子
DD : 死亡结构域
DISC : 死亡诱导信号复合体
DED : 死亡效应结构域
TNFR : 肿瘤坏死因子受体
TRAIL : TNF相关调亡诱导配体
简写
introduction
The caspase family is well characterized as playing a crucial role in modulation of programmed cell death (PCD), which is a ically regulated, evolutionarily conserved process with numerous links to many human diseases, most notably cancer.
introduction
There are two types of apoptotic caspases: initiator caspases and executioner caspases.
Initiator caspases: casp2, casp8, casp9 and casp10
executioner caspases: casp3, casp6, casp7
caspases
introduction
Caspases are involved in two different apoptotic
pathways :
the death-receptor pathway (extrinsic), which is triggered by ligation of death receptors and subsequent caspase-8 activation.
(ii) the mitochondrial pathway (intrinsic), which is
initiated by intracellular stress, and subsequent-ly activated by caspase-9.
Ⅰ Caspase-mediated apoptosis in cancer
ⅰ Tumour necrosis fact or receptors
ⅱ Bcl-2 family
ⅲ Other apoptotic modulators: cytochrome c, Apaf-1 and IAPs
Ⅱ Caspase-mediated autophagy in cancer
Ⅲ Targeted caspases and their substrates for drug discovery
ⅰ Caspase- 8, -9 and -3
ⅱ PARP -1 and Beclin-1
1 Caspase-mediated apoptotic pathways in cancer
Tumour necrosis fact or receptors
During this process, Fas ligand(FasL), which triggers trimerization of receptors and aggregation of intra-cellular death domains
(DDs) , leads to formation of a death- inducing plex (DISC ) . The death adaptor protein FADD
and photolytic enzyme caspase-8 are recruited to Fas.
The Bcl-2 family is pivot al for regulation of apoptosis , and includes both anti- and pro-apoptotic proteins.
Bcl-2 family
Bcl-2 family
截图 2