Caspase functions and structure A Sequence Function homology apoptosis other 12 11 infiammation 13 infiammation 2 initiator/effector? Precursor Active enzy 9 initiator 8 initiator prodomain large small 6 effector 3 effecto AspX Asp Ix 7 effector low gh 10 initiator? Sequence homology amon caspases catalytic stes
Caspase functions and structure
Classification of Caspases Active Activation mogen length and motif subunits adapter preference Apoptotic initiators Caspase-2 (51) Long 20/12 RAIDD DYD. Caspase-8(55) Long, DI 8/11 FADD ADEYI Caspase-9 (45) Long, CARD 17/10 APAF-1 I/V/L)EHD Caspase-10(55) Long DED 7/12 FADD Unknown Apoptotic executioners Caspase-3 (32) Short 17/12 Caspase-6(34) Short 18/11 Short 20/12 DEXD Cytokine processors Long, CARD 0/10 ?CARDIAK w/YF正H Caspase(43) Long, CARd 20/10 (/)EHD 20/10 mCaspase-11(42) Long 20/10 Unknown Unknown mCaspase-12(50) 20/10 Unknown Unknown Caspase-13(43) 20/10 Unknown Unknown mCaspase-14(30 Short 20/10 Unknown Invertebrate caspases CED-3(5 Long, CARD 7/14 CED4 DEXD DCP1(36) Short 22/13 NA Unknown The tetrapeptides are lsted in the P4-Pi direction Proteolysis occurs solely after the Pi aspartate
Classification of Caspases
半胱天冬酶的特征 前功能域活性激活作用优先作用 酶原 别名 长度亚单位」接头蛋自[四肽 (kDa) 和基序 KDa 凋亡启动因子ICH-1样半胱天冬酶-2亚家族 半胱天冬酶-2(51) ICH-I 长CARD20/12 RAIDD DXXD 半胱天冬酶8(1) FLICE, MACH, Mch5长DD⊥18/FAD(DEXD 半胱天冬酶-9(45) ICE-LAP 6 Mch 6 K, CARD 17//10 APAF-1(I/V/L)EHD 半胱天冬酶-10(55) Mch 长,DED17/12 FADD 不明 凋亡执行因子CPP32样半胱天冬酶-3亚家族 半胱天冬酶-3(32) CPP32, Yama, apopain 短短短 17/12 不需 DEXD 半胱天冬酶-6(34) Mch2 l8/11 不需(w/T/)EXD 半胱天冬酶-7(35)Mch3, ICE-LAR3,CMH-1 20/12 不需DEXD 细胞因子加工因子ICE样半胱天冬酶-1亚家族 半胱天冬酶-1(45) ICE k CARD 20//10?CARDIAK(W/Y/FEHD 半胱天冬酶-4(43) I CEreal-Ⅱ, TX ICH2长CARD20/10不明(W//F)EHD 半胱天冬酶-5(48) ICErel-IIL. TY 20/10 不明(w//F)EH m半胱天冬酶-11(42) 20/10不明 不明 m半胱天冬酶-12(50) 20/12不明 不明 半胱天冬酶-13(43) 长长长短 20/12 不明 不明 「m半胱天冬酶-14(30) 20/12不需 不明 无脊椎动物半胱天冬酶 CED-3(56) 长CARD CED-4 DEXD DCP-1(36 22//13 不需 不明
半胱天冬酶的特征 前功能域 活性 优先作用 酶原 别名 长度 亚单位 四肽 (kDa) 和基序 kDa 序列a 凋亡启动因子 ICH-1样 半胱天冬酶-2 亚家族 半胱天冬酶-2 (51) ICH-1 长,CARD 20//12 RAIDD DXXD 半胱天冬酶-8 (51) FLICE, MACH, Mch5 长,DED 18//11 FADD (I/V/D)EXD 半胱天冬酶-9 (45) ICE-LAP 6, Mch 6 长,CARD 17//10 APAF-1 (I/V/L)EHD 半胱天冬酶-10 (55) Mch4 长,DED 17//12 FADD 不明 凋亡执行因子 CPP32样 半胱天冬酶-3 亚家族 半胱天冬酶-3 (32) CPP32,Yama, apopain 短 17//12 不需 DEXD 半胱天冬酶-6 (34) Mch2 短 18//11 不需 (V/T/I)EXD 半胱天冬酶-7 (35) Mch3,ICE-LAP3, CMH-1 短 20//12 不需 DEXD 细胞因子加工因子 ICE样 半胱天冬酶-1 亚家族 半胱天冬酶-1 (45) ICE 长,CARD 20//10 ?CARDIAK (W/Y/F)EHD 半胱天冬酶-4 (43) ICErel-Ⅱ, TX, ICH-2 长,CARD 20//10 不明 (W/L/F)EHD 半胱天冬酶-5 (48) ICErel-Ⅲ, TY 长 20//10 不明 (W/L/F)EHD m半胱天冬酶-11(42) 长 20//10 不明 不明 m半胱天冬酶-12(50) 长 20//12 不明 不明 半胱天冬酶-13(43) 长 20//12 不明 不明 m半胱天冬酶-14(30) 短 20//12 不需 不明 无脊椎动物半胱天冬酶 CED-3 (56) 长,CARD 17//14 CED-4 DEXD DCP-1b (36) 短 22//13 不需 不明 激活作用 接头蛋白
Caspase-deficient mice Knockout Phenotype Caspase-1 Viable; impaired processing of IL-1; resistant to endotoxic shock Caspase-2 Viable; excess numbers of female germ cells; oocytes resistant to chemotherapeutic drugs; B lymphoblasts resistant to granzyme B accelerated death of facial neurons during development and of sympathetic neurons deprived of NGF Caspase-3 Lethality at 3-5 weeks of age; defective neuronal apoptosis; T cells resistant to antigen-induced death; abnormal apoptotic morphology in dying cells Caspase-8 Lethality around E12. 5; hyperemia and abnormal heart muscle development; MEFS resistant to TNF, Fas and DR3 but sensitive to UVirradiation, etoposide, staurosporine, serum deprivation Caspase-9 Perinatal lethal; impaired neuronal apoptosis ES cells, MEFs and thymocytes generally resistant to intrinsic death stimuli such as DNA damage, though resistance depends on cell type Caspase-11 Viable; impaired processing of caspase-1, IL-1; resistant to endotoxic shock Caspase-12 Viable; embryonic fibroblasts are resistant to ER stress
Caspase-deficient mice Knockout Phenotype Caspase-1 Viable; impaired processing of IL-1; resistant to endotoxic shock. Caspase-2 Viable; excess numbers of female germ cells; oocytes resistant to chemotherapeutic drugs; B lymphoblasts resistant to granzyme B; accelerated death of facial neurons during development and of sympathetic neurons deprived of NGF. Caspase-3 Lethality at 3–5 weeks of age; defective neuronal apoptosis; T cells resistant to antigen-induced death; abnormal apoptotic morphology in dying cells. Caspase-8 Lethality around E12.5; hyperemia and abnormal heart muscle development; MEFs resistant to TNF, Fas and DR3 but sensitive to UV irradiation, etoposide, staurosporine, serum deprivation. Caspase-9 Perinatal lethal; impaired neuronal apoptosis; ES cells, MEFs and thymocytes generally resistant to intrinsic death stimuli such as DNA damage, though resistance depends on cell type. Caspase-11 Viable; impaired processing of caspase-1, IL-1; resistant to endotoxic shock. Caspase-12 Viable; embryonic fibroblasts are resistant to ER stress
Caspases activation Death receptor pathway: caspase 8 .Mitochondrial pathway: caspase 9 .ER stress pathway: caspase 12 Fas lie FADD Procaspase-8 Procaspase-9 Mitochondrion ase-8 Initiator caspases Caspases Apoptosome Proca 3 Caspase-3 Effector caspases Apoptosis Nature Reviews Molecular Cell Biology
Caspases activation •Death receptor pathway: caspase 8 •Mitochondrial pathway: caspase 9 •ER stress pathway: caspase 12 (CAD: caspase-activated deoxyribonulease)