ライフサイエンスコーパス: procaspase 8

1 in-null cells up-regulates the expression of procaspase 8.

2 , whereas the death effector domain binds to procaspase 8.

3 reas the FADD death effector domain binds to procaspase 8.

4 binding do not affect the binding of E6* to procaspase 8.

5 so bind to and accelerate the degradation of procaspase 8.

6 known as E6* results in the stabilization of procaspase 8.

7 o decrease the TNF-alpha-induced cleavage of procaspase-8.

8 ine, however, did not affect the cleavage of procaspase-8.

9 FADD then binds and activates procaspase-8.

10 cl-xL and the activation of procaspase-3 and procaspase-8.

11 Bap31 and is required for the activation of procaspase-8.

12 IKK1 protein degradation or interaction with procaspase-8.

13 rosis factor (TNF)-alpha-induced cleavage of procaspase-8, -9, and -3 and poly(ADP-ribose) polymerase

14 h this finding, processing and activation of procaspases-8, -9, and -3 were markedly diminished and d

15 gly, loss of menin reduces the expression of procaspase 8, a critical protease that is essential for

16 * binding on the expression and stability of procaspase 8, a key mediator of the apoptotic pathway.

17 echanisms may involve other caspases such as procaspase-8, a 55 kDa apical caspase, which we found co

18 show that the detachment-induced cleavage of procaspase-8, a newly described mediator of cellular adh

19 Canstatin-induced procaspase 8 activation and cell death were also inhibit

20 , we show that Y380 phosphorylation inhibits procaspase-8 activation at the CD95 DISC, thereby preven

21 cells and disrupts TRAIL/CD95 DISC-mediated procaspase-8 activation in a functional DISC reconstitut

22 ose a unified mechanism for DED assembly and procaspase-8 activation in the regulation of apoptotic a

23 lso highly susceptible to cleavage, and that procaspase-8 activation is a linear process without self

24 Procaspase-8 activation is regulated by the ratio of unb

25 gnaling complex (DISC) and potently promotes procaspase-8 activation through hetero-dimerization.

26 eath, c-FLIP(L) is also capable of enhancing procaspase-8 activation through heterodimerization of th

27 aspect of c-FLIP(L) function that modulates procaspase-8 activation to elicit diverse responses in d

28 ti-apoptotic (c-FLIPL/c-FLIPS) regulators of procaspase-8 activation.

29 8:c-FLIPS lacks activity and potently blocks procaspase-8 activation.

30 C), but strikingly increased DISC-associated procaspase-8 activation.

31 by co-immunoprecipitation using Fas and anti-procaspase-8 after ischemia.

32 cleavage of procaspase-3, procaspase-9, and procaspase-8, along with the known caspase targets p21-a

33 Procaspase-8, an initiator caspase recruited to death re

34 Biochemical analysis demonstrates that both procaspase 8 and active caspase 8 are localized mainly o

35 fluorescence microscopy, however, shows that procaspase 8 and active caspase 8 predominantly colocali

36 ring RNA leads to increases in the levels of procaspase 8 and its binding to both itself and FADD.

37 th effector domain (DED) engages the DEDs of procaspase 8 and its inhibitor FLIP to form death-induci

38 sitive to the steady state concentrations of procaspase 8 and its negative regulator, Bar, but not th

39 ptosis, as shown by Western blot analysis of procaspase 8 and poly(ADP-ribose) polymerase cleavage af

40 nd IETD(OMe)-fmk, nor with the expression of procaspase-8 and -9, apoptotic protease activating facto

41 cancer cells, leading to initial cleavage of procaspase-8 and activation of subsequent downstream eve

42 Furthermore, BAR can bridge procaspase-8 and Bcl-2 into a protein complex.

43 were also associated with the processing of procaspase-8 and Bid (cytosolic, proapoptotic BH3 domain

44 ibitor zIETD-fmk inhibited the processing of procaspase-8 and Bid but did not inhibit the cytosolic a

45 ced mitochondrial dysfunction, activation of procaspase-8 and Bid, and apoptosis in Bcl-2- and Bcl-xL

46 s also associated with greater processing of procaspase-8 and Bid, as well as greater cytosolic accum

47 ted death domain, and enhanced activation of procaspase-8 and cleavage of its substrate Bid.

48 sing the DEDs contained in the prodomains of procaspase-8 and procaspase-10 and isolated a DED-associ

49 sitive cells were capable of processing both procaspase-8 and procaspase-3 into active subunit forms,

50 cellular domain of CD95 and the prodomain of procaspase-8 and reveal a self-association surface neces

51 owever, inhibit Fas-induced cleavage of both procaspase-8 and the pro-apoptotic protein Bid, indicati

52 nal DISC using only purified CD95, FADD, and procaspase-8 and unveil a two-step activation mechanism

53 proper oligomerization and autoactivation of procaspase-8 and/or procaspase-10 during T lymphocyte ac

54 nduced T cell death, increased activation of procaspases 8 and 3, and loss of mitochondrial transmemb

55 Canstatin-induced activation of procaspases 8 and 9 as well as the induced reduction in

56 lso induces Fas ligand expression, activates procaspases 8 and 9 cleavage, reduces mitochondrial memb

57 adaptor protein FADD, the initiator caspases procaspases-8 and -10 and the regulatory protein c-FLIP.

58 caspase-family cell death proteases, namely procaspases-8 and -10.

59 pathway which is independent of FasL, FADD, procaspase 8, and DISC.

60 FADD (Fas-associated death domain protein), procaspase 8, and p53 were not affected.

61 associated protein with death domain (FADD), procaspase-8, and cellular FLICE-inhibitory proteins (cF

62 s and cell death regulation, dimerization of procaspase-8, and inhibition of caspase-8 pathways, whic

63 DEDAF interacts with FADD, procaspase-8, and procaspase-10 in the cytosol as well a

64 th processing of procaspase-3, procaspase-7, procaspase-8, and procaspase-9 and with cleavage of Bid

65 rves as a platform to activate the initiator procaspase-8, and thereby bridges two critical organelle

66 ascade through binding of the DED domains of procaspase-8; and a C-terminal death domain (DD).

67 Finally, K1 transfectants cleaved procaspase 8 at significantly lower rates than did K1m t

68 ter TRAIL treatment and enhanced cleavage of procaspase-8 at the death-inducing signaling complex.

69 ation attenuates DISC activity by inhibiting procaspase-8 autoproteolytic activity but not recruitmen

70 tosis correlated with sequential cleavage of procaspase 8, BID, procaspase 9, and procaspase 3.

71 o induced the processing of procaspase-9 and procaspase-8, Bid cleavage, and apoptosis.

72 thesis and was associated with activation of procaspase-8, Bid cleavage, and release of cytochrome c

73 peptide inhibitors that can block E6(large)/procaspase 8 binding do not affect the binding of E6* to

74 Ds suggested a specific region for E6(large)/procaspase 8 binding, which was subsequently confirmed b

75 -p-nitroanilide [IETD]) or dominant negative procaspase 8 blocked the potentiation of bile acid-induc

76 a protein fragment generated by cleavage of procaspase 8 by human immunodeficiency virus (HIV) prote

77 l the key steps leading to the activation of procaspase-8 by oligomerization.

78 Thus, procaspase-8:c-FLIPL exhibits localized enzymatic activi

79 spase-8, which determines composition of the procaspase-8:c-FLIPL/S heterodimer.

80 ated procaspase-8 oligomer assembly, whereas procaspase-8:c-FLIPS lacks activity and potently blocks

81 elical filament is required to orientate the procaspase-8 catalytic domains, enabling their activatio

82 er expression of TRAIL-R1/DR4, TRAIL-R2/DR5, procaspase 8, cFLIP-L, cFLIP-s, Bax, Bcl-xL, or Bax.

83 present the atomic coordinates of human FADD-procaspase-8-cFLIP complexes, revealing structural insig

84 A helical procaspase-8-cFLIP hetero-double layer in the complex ap

85 Procaspase 8 cleavage and activity of the apoptosis-asso

86 tory protein long (cFLIP(L)), which prevents procaspase-8 cleavage into active caspase-8.

87 e lifespan of infected monocytes by blocking procaspase-8 cleavage, yet the precise viral mechanism r

88 ve oxygen species generation, with resulting procaspase-8 cleavage.

89 We show that ASC filaments in turn nucleate procaspase-8 death effector domain (DED) filaments in vi

90 monstrate that the residues that mediate E6*/procaspase 8 DED binding localize to a different region

91 f FLIP DED1 and the alpha2/alpha5 surface of procaspase 8 DED2.

92 Mutating key interacting residues in procaspase-8 DED2 abrogates DED chain formation in cells

93 Sequence similarities between the FADD and procaspase 8 DEDs suggested a specific region for E6(lar

94 4-HNE induces Fas-dependent apoptosis in procaspase 8-deficient Jurkat cells via the activation o

95 inding to the DISC is instead a co-operative procaspase-8-dependent process.

96 ecruited to the DISC at comparable levels to procaspase 8 despite lower cellular expression.

97 hr in culture, Fas ligand expression and Fas-procaspase-8 DISC assembly increased, and by 72 hr, cell

98 Interestingly, we observed condensation of procaspase-8 filaments containing the catalytic domain,

99 Procaspase-8 filaments may also be relevant to apoptosis

100 ls assume that c-FLIP directly competes with procaspase-8 for recruitment to FADD.

101 LRARalpha recruited c-FLIP(L/S) and excluded procaspase 8 from Fas death signaling complex.

102 lls from programmed cell death by preventing procaspase-8 from proteolytic cleavage.

103 DD green fluorescent protein (GFP) and C360S procaspase 8-GFP to the plasma membrane.

104 r the alpha1/alpha4 surface of FADD, whereas procaspase 8 has preferential affinity for FADD's alpha2

105 Recent studies have revealed that procaspase-8 has an important function in cell adhesion

106 erminants that favor heterodimerization over procaspase-8 homodimerization, and induce the latent act

107 Similar mutations in procaspase 8 impair the ability of HIV to kill infected

108 ypes 6b and 11, alters the cellular level of procaspase 8 in a dose-dependent manner.

109 modulate both the level and the activity of procaspase 8 in opposite directions.

110 ction with one, but not both, of the DEDs of procaspase-8 in a perpendicular arrangement.

111 lectron microscopy, we visualize full-length procaspase-8 in complex with FADD.

112 0 facilitated the cleavage and activation of procaspase-8 in TRAIL-resistant cells, confirming that i

113 rved in intron 8 of the CASP8 gene (encoding procaspase-8) in association with cutaneous basal-cell c

114 nce was mediated by interaction of S-3B with procaspase-8, inhibiting death-inducing signaling comple

115 rk shows that inflammasomes can also recruit procaspase-8, initiating apoptosis.

116 The DEDs of FADD, FLIP and procaspase 8 interact with one another using two binding

117 howed that interaction surfaces that mediate procaspase-8 interaction overlap with those required for

118 human brain, because Fas expression plus Fas-procaspase-8 interaction were robust in contused cortica

119 D-Fas-associated death domain protein (FADD)-procaspase-8 interaction.

120 aining the catalytic domain, suggesting that procaspase-8 interactions within and/or between filament

121 In its migratory role, procaspase-8 interacts with the phosphatidylinositol-3-O

122 1, which in turn catalyzes the conversion of procaspase-8 into active caspase-8.

123 signaling complex components (DR5, FADD, and procaspase-8) into cholesterol-rich and ceramide-rich do

124 tudies have suggested that the activation of procaspase-8 is mediated by cross-cleavage of precursor

125 DD (FAS-associated death domain protein) and procaspase 8, leading to direct activation of caspase 3,

126 g FLICE-inhibitory protein (FLIP), and lower procaspase-8 levels were present in TRAIL-resistant cell

127 ar FLICE-like inhibitory protein (c-FLIP), a procaspase-8-like apoptotic regulator, plays an essentia

128 ression of the viral DEDs strongly inhibited procaspase-8-mediated NF-kappaB activation, an event not

129 e propose an alternative DISC model in which procaspase-8 molecules interact sequentially, via their

130 the enzymatic properties of caspase-8; while procaspase-8 molecules specifically process one another,

131 re susceptible to processing than individual procaspase-8 molecules, which leads to their cross-cleav

132 ling, as cellular expression of noncleavable procaspase-8 mutants, which undergo DISC-mediated oligom

133 the binding of the smaller isoform, E6*, to procaspase 8 occurs at a different region, as deletion a

134 ntially an activator, promoting DED-mediated procaspase-8 oligomer assembly, whereas procaspase-8:c-F

135 spase-3 activation required co-expression of procaspase-8 or -10.

136 ase expression of DR4/DR5, or recruitment of procaspase-8 or FADD to the death-inducing signaling com

137 Forced expression of procaspase-8 or FLIP antisense oligonucleotides also sen

138 as-associated protein with death domain, and procaspase-8 or procaspase-10; receptor interacting prot

139 e heightened expression of BCL-2 relative to procaspase 8, possibly explaining the persistence of HIV

140 e of the intersubunit linker of c-FLIP(L) by procaspase-8 potentiates the activation process by enhan

141 ical and bioinformatics tools, we identified procaspase-8 (procasp8), the caspase-8 zymogen, as a cyt

142 Soluble factor(s) attenuated procaspase-8, procaspase-3, and poly(ADP-ribose) polymer

143 the death-inducing signal complex prevented procaspase-8 processing and activation of the effector p

144 at physiologically relevant levels enhances procaspase-8 processing in the CD95 DISC and promotes ap

145 the presence of CCCP and decreased initiator procaspase-8 processing, indicating that additional proc

146 Here we show that dimerization of procaspase-8 produces enzymatically competent precursors

147 omain, which associates efficiently with the procaspase-8 protease domain and induces the enzymatic a

148 ugh the stable homophilic interaction of the procaspase-8 protease domain.

149 s in its association with the DED-containing procaspase-8 protein, a cellular apoptosis precursor pro

150 arkedly reduced in cells that contain little procaspase-8 protein, suggesting that this apical protea

151 02), procaspase-3 (R(s) = 0.56, P <.006) and procaspase-8 (R(s) = 0.64, P <.002).

152 of Fas-associated death domain protein, and procaspase 8 recruited to the death-inducing signaling c

153 s-induced apoptosis at the level of FADD and procaspase-8, respectively.

154 ctor (TNF) R1, the adaptor protein FADD, and procaspase 8 results in a significant modification of th

155 nor were there detectable levels of FADD or procaspase-8 seen in the signaling complex.

156 ial findings that the two E6 isoforms affect procaspase 8 stability in an opposing manner.

157 e by way of alternate splicing, can modulate procaspase 8 stability.

158 Interaction between ASC PYD and procaspase-8 tandem DEDs optimally required both DEDs an

159 oth dimerization and proteolytic cleavage of procaspase-8 that is obligatory for death-receptor-induc

160 Intriguingly, although both isoforms bind to procaspase 8, the large isoform accelerates the degradat

161 lar level, and consequently the activity, of procaspase 8, thus modifying the cellular response to cy

162 mmunodeficiency virus (HIV) protease cleaves procaspase 8 to a fragment, termed Casp8p41, that lacks

163 Binding leads to a change in the ability of procaspase 8 to bind either to itself or to FADD (Fas-as

164 ate that HIV-1 protease specifically cleaves procaspase 8 to create a novel fragment termed casp8p41,

165 an involve HIV protease-mediated cleavage of procaspase 8 to generate a fragment (Casp8p41) that dire

166 d that HIV protease cleaves the host protein procaspase 8 to generate Casp8p41, which can bind and ac

167 ypoxia-ischemia, in concert with cleavage of procaspase 8 to its active form.

168 Despite recruitment of procaspase 8 to the plasma membrane by both bile acids,

169 1 to form a HIPPI/HIP1 complex that recruits procaspase-8 to begin the process of apoptosis.

170 f the Fas-associated death domain (FADD) and procaspase-8 to form the death-inducing signaling comple

171 cruitment of Fas-associated death domain and procaspase-8 to the death-inducing signaling complex aft

172 nt of Fas-associated death domain (FADD) and procaspase-8 to the Fas receptor was examined via analys

173 uence of PKC on recruitment of both FADD and procaspase-8 to the Fas receptor.

174 Moreover, we show that the recruitment of procaspase-8 to the Fis1-Bap31 platform is an early even

175 iants lacking Fas-associated death domain or procaspase-8 undergo tipifarnib-induced apoptosis, where

176 ges FLIP using its alpha1/alpha4 surface and procaspase 8 using its alpha2/alpha5 surface; these trip

177 n vitro DISC model together with recombinant procaspase-8 variants, we show that Y380 phosphorylation

178 cognition receptors recruit procaspase-1 and procaspase-8 via the adaptor protein ASC.

179 Procaspase 8 was undetectable by immunoblotting in whole

180 At the time of DISC assembly, procaspase-8 was cleaved and the cleavage product appear

181 Constitutive expression of procaspase-8 was detectable in most cortical neurons, an

182 osis by preventing proteolytic activation of procaspase-8, we define pUL36 as a multifunctional inhib

183 cking Fas-associated death domain protein or procaspase-8 were resistant to CI-1040-induced apoptosis

184 gulated by the ratio of unbound c-FLIPL/S to procaspase-8, which determines composition of the procas

185 FADD initially recruits procaspase-8, which in turn recruits and heterodimerizes

186 his function by preventing the conversion of procaspase-8, which is an adhesion/migration factor, to

187 large isoform accelerates the degradation of procaspase 8 while the small isoform stabilizes it.

188 Initially, dimerization yields active procaspase-8 with a very restricted substrate repertoire

189 The association of procaspase-8 with the Fis1-Bap31 complex is dependent on