ライフサイエンスコーパス: procaspase

1 , may alter the substrate specificity of the procaspase.

2 vival through its cytosolic association with procaspases.

3 omplexes, which facilitate the maturation of procaspase 1 to caspase 1, leading to IL-1beta and IL-18

4 NLRC5, together with procaspase 1, pro-IL-1beta, and the inflammasome adaptor

5 IL18) or close to genes that are involved in procaspase-1 activation (NLRC4 and CARD16, CARD17, and C

6 tion-defective NLRC4 S533A failed to recruit procaspase-1 and did not assemble inflammasome specks du

7 osolic pattern recognition receptors recruit procaspase-1 and procaspase-8 via the adaptor protein AS

8 danger signals, triggering self-cleavage of procaspase-1 and production of the proinflammatory cytok

9 ypically a Nod-like receptor), the precursor procaspase-1 and the adaptor ASC.

10 In a transfection model, such variant procaspase-1 binds receptor interacting protein kinase 2

11 In conclusion, variant procaspase-1 binds RIP2 and thereby activates NF-kappaB.

12 Finally, C1q decreased procaspase-1 cleavage and caspase-1-dependent cleavage o

13 ither WT or enzymatically inactive (p.C284A) procaspase-1 fusion reporter proteins.

14 large oligomeric filaments, which facilitate procaspase-1 recruitment.

15 ereby activates NF-kappaB, whereas wild-type procaspase-1 reduces intracellular RIP2 levels by enzyma

16 CD44 ECD-shedding reduced the conversion of procaspase-1 to active caspase-1, caspase-1 activity and

17 me in the nuclei and interacted with ASC and procaspase-1 to form a functional inflammasome.

18 via a homotypic PYD interaction and recruits procaspase-1 via a homotypic caspase recruitment domain

19 expression of pro-IL-1beta, NLRP3, ASC, and procaspase-1 was not affected in Pml(-/-) macrophages.

20 uences of increased myocardial expression of procaspase-1 were examined on the normal and ischemicall

21 bridging NLRP proteins, such as NLRP3, with procaspase-1 within the inflammasome complex, which subs

22 esented here is the crystal structure of the procaspase-1 zymogen without its caspase recruitment dom

23 RP3 inflammasome components (NLRP3, ASC, and procaspase-1) and pro-IL-1beta in ARPE-19 cells.

24 h a caspase recruitment domain) and effector procaspase-1, resulting in active caspase-1 formation wh

25 NLRP3 promotes clustering and activation of procaspase-1.

26 cells were found to express NLRP3, ASC, and procaspase-1.

27 ic speck-containing protein with a card) and procaspase-1.

28 , a response that requires the activation of procaspase-1.

29 is the activation of the initiator caspase, procaspase-1.

30 ion of a multiprotein complex that activates procaspase-1.

31 omprises a sensor, an adaptor, and a zymogen procaspase-1.

32 cular glue between danger-signal sensors and procaspase-1.

33 ciency selectively reduced the processing of procaspase-1.

34 n containing CARD), and the effector protein procaspase-1.

35 nd cellular stress signals via activation of procaspases-1 and -8.

36 caspase 9 processing, increased induction of procaspase 11, and decreased processing of caspase 12 in

37 substrates, including the apoptotic molecule procaspase 12 and podocyte cytoskeletal protein talin 1.

38 In this study, cleavage of procaspase 12 preceded that of caspases 3 and 9 after ci

39 he ER cytochrome P450 leads to activation of procaspase 12, resulting in apoptosis.

40 demonstrated activation of the UPR-specific procaspase-12 and the increased presence of ROS, whereas

41 blot analysis revealed that the quantity of procaspase-12 is actually higher in serum-starved cells

42 Procaspase-12 was cleaved into its active form after tre

43 f the hippocampal CA1 subregion and preceded procaspase-2 activation after tGCI.

44 s imply that PIDD plays an important role in procaspase-2 activation and delayed CA1 neuronal death a

45 xpression of PIDD-CC, but also activation of procaspase-2 and Bid, resulting in a decrease in histolo

46 tudies demonstrated that PIDD-CC, RAIDD, and procaspase-2 were co-localized and bound directly, which

47 ous protein with a death domain (RAIDD), and procaspase-2.

48 Treatment of cardiomyocytes with procaspase 3 activating compound 1, a small-molecule act

49 However, procaspase 3 cleavage was undetectable, suggesting that

50 treated cells, and purified tTGase catalyzes procaspase 3 cross-linking in vitro.

51 ctive GST-US3(K220N) protein, phosphorylated procaspase 3 in vitro.

52 NIP3 and the ratio of activated caspase 3 to procaspase 3 increased after LVAD support, Bcl-2 and TUN

53 e either transfected with a plasmid encoding procaspase 3 or superinfected with a proapoptotic mutant

54 raphane treatment also increases cleavage of procaspase 3, 8, and 9 and enhances PARP cleavage and ap

55 ctive caspase 3 from the transfected zymogen procaspase 3, concomitant with inhibition of apoptosis.

56 mary CLL cells express high levels of latent procaspases (3, -7, and -9).

57 exhibited significant increases in synaptic procaspase- 3 and active caspase-3 expression levels tha

58 Procaspase-3 (P3) and procaspase-7 (P7) are activated th

59 the design and discovery of next-generation procaspase-3 activating compounds, and sheds light on th

60 ls a strong correlation between the in vitro procaspase-3 activating effect and their ability to indu

61 Smac prevented cIAP1 from inhibiting procaspase-3 activation and reversed the inhibition by p

62 ity for procaspase-3, which is important for procaspase-3 activation at the physiological concentrati

63 Inhibition of procaspase-3 activation depended on BIR2 and BIR3 of cIA

64 we interrogate the biochemical mechanism of procaspase-3 activation on 1541 fibrils in addition to p

65 rocessing and was a more potent inhibitor of procaspase-3 activation than of already activated caspas

66 essed caspase-9 in the apoptosome and blocks procaspase-3 activation.

67 Combinations of procaspase-3 activators PAC-1 and 1541B show considerabl

68 ing for further evaluation of small-molecule procaspase-3 activators, including S-PAC-1, a compound t

69 scovery of a compound, PAC-1, which enhances procaspase-3 activity in vitro and induces apoptotic dea

70 o previous reports, we find no evidence that procaspase-3 alone is capable of self-activation, consis

71 Notably, we show that the proenzymes procaspase-3 and -9 are basally persulfidated in resting

72 pase-9 in PAI-1-/- EC led to lower levels of procaspase-3 and cleaved caspase-3, thereby promoting su

73 Similar to PAC-1, S-PAC-1 activated procaspase-3 and induced cancer cell apoptosis.

74 reduced cell viability, increased necrosis, procaspase-3 and PARP processing, caspase-3 activity, an

75 densation of chromatin, and cleavage of both procaspase-3 and PARP.

76 ng, membrane blebbing, cytochrome c release, procaspase-3 and poly(ADP-ribose)polymerase (PARP) cleav

77 that zinc inhibits the enzymatic activity of procaspase-3 and that PAC-1 strongly activates procaspas

78 a specific transnitrosation reaction between procaspase-3 and thioredoxin-1 (Trx) occurs in cultured

79 ty have been examined, comparable studies on procaspase-3 are lacking.

80 Specifically, PR3 cleaved procaspase-3 at a site upstream of the canonical caspase

81 ition of catalytic activity upon cleavage of procaspase-3 at Asp(175).

82 Hence, cIAP1 prevented the activation of procaspase-3 but had no effect on the processing of proc

83 membrane permeabilization (LMP), leading to procaspase-3 cleavage and apoptosis.

84 rocaspase-9 processing as well as downstream procaspase-3 cleavage in several cell types and under mu

85 l hallmarks of apoptosis, such as PARP-1 and procaspase-3 cleavage.

86 otein, cytochrome c release, and predominant procaspase-3 cleavage.

87 caspase-3 or other initiator proteases with procaspase-3 dramatically stimulates maturation of the p

88 ibrils can serve as platforms to concentrate procaspase-3 for trans-activation by upstream proteases.

89 ocaspase-3 and that PAC-1 strongly activates procaspase-3 in buffers that contain zinc.

90 , stimulate rapid and dramatic maturation of procaspase-3 in multiple cancer cell lines, and powerful

91 ) was reported that enhances the activity of procaspase-3 in vitro and induces apoptotic death in can

92 combined data indicate that PAC-1 activates procaspase-3 in vitro by sequestering inhibitory zinc io

93 ntal evidence indicates that PAC-1 activates procaspase-3 in vitro through chelation of inhibitory zi

94 541B show considerable synergy in activating procaspase-3 in vitro, stimulate rapid and dramatic matu

95 in is the mechanism by which PAC-1 activates procaspase-3 in vitro.

96 ns an RGD motif, which potentially activates procaspase-3 intracellular and or binds to integrins.

97 During maturation, procaspase-3 is cleaved at D175, which resides in a link

98 However, the measured Km of C9Holo for procaspase-3 is much lower than that of LZ-C9.

99 Interestingly, procaspase-3 levels are often elevated in cancer cells,

100 ion of the denitrosylation of S-nitrosylated procaspase-3 mediated by the redox protein Trx2 is a par

101 and mouse granzyme B cleave species-specific procaspase-3 more efficiently than the unmatched substra

102 nitrated cytochrome c and interaction with a procaspase-3 subunit was assayed.

103 nalyses identified a cluster of mutations in procaspase-3 that resist small-molecule activation both

104 estering inhibitory zinc ions, thus allowing procaspase-3 to autoactivate itself to caspase-3.

105 d that directly stimulates the activation of procaspase-3 to caspase-3 could selectively induce apopt

106 o apoptosis is the activation of the zymogen procaspase-3 to caspase-3.

107 embles into nanofibrils, and localization of procaspase-3 to the fibrils promotes activation.

108 unique biocatalytic material that activates procaspase-3 via induced proximity.

109 cell differentiation from bone marrow cells, procaspase-3 was present in cells of all stages of matur

110 lex (and thus loses its capacity to activate procaspase-3) dictates how fast the timer 'ticks' over.

111 h purified recombinant Apaf-1, procaspase-9, procaspase-3, and cytochrome c from horse heart.

112 Soluble factor(s) attenuated procaspase-8, procaspase-3, and poly(ADP-ribose) polymerase cleavage a

113 ancer cells through the direct activation of procaspase-3, has implications for the design and discov

114 y using purified ProT, Apaf-1, procaspase-9, procaspase-3, Hsp70, cytochrome c, PHAPI, CAS, and regul

115 hain Fv antibody fragment, fused to inactive procaspase-3, induced auto-activation of caspase-3 after

116 re caspase-3 is >10(7)-fold more active than procaspase-3, making this proenzyme a remarkably inactiv

117 Apoptosis was associated with processing of procaspase-3, procaspase-7, procaspase-8, and procaspase

118 ement mechanism, so that unlike the effector procaspase-3, procaspase-9 cannot be processed by the ap

119 ) that stimulates activation of a proenzyme, procaspase-3, to generate mature caspase-3.

120 ally promotes the maturation of the zymogen, procaspase-3, to its mature form, caspase-3.

121 ates caspase-9 by enhancing its affinity for procaspase-3, which is important for procaspase-3 activa

122 e 2 (TG2), which cross-links and inactivates procaspase-3.

123 r se contributed little to the activation of procaspase-3.

124 n of the active caspase-3 from its precursor procaspase-3.

125 than C9Holo for the physiological substrate procaspase-3.

126 heterodimer that more efficiently activated procaspase-3.

127 cells when each variable region is fused to procaspase-3.

128 by chelation of labile inhibitory zinc from procaspase-3.

129 directly activate proenzymes, the apoptotic procaspases-3 and -6.

130 One such target, the 40 kDa procaspase 4 is significantly upregulated at the protein

131 criptional control, Bax, Bad, Puma, Bid, and procaspase 6, accompanied by reduced anti-apoptotic Bcl-

132 changes in the conformational flexibility of procaspase-6 at the discrete states that reflect the ser

133 S-3B binding to procaspase-6 inhibited its activation despite mitochondr

134 rapy, in this case through interactions with procaspase-6.

135 Procaspase-3 (P3) and procaspase-7 (P7) are activated through proteolytic matu

136 associated with processing of procaspase-3, procaspase-7, procaspase-8, and procaspase-9 and with cl

137 he latter complex directly cleaves/activates procaspase-7.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

173 4-HNE induces Fas-dependent apoptosis in procaspase 8-deficient Jurkat cells via the activation o

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

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

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

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

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

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

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

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

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

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

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

185 8:c-FLIPS lacks activity and potently blocks procaspase-8 activation.

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

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

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

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

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

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

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

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

194 Procaspase-8 filaments may also be relevant to apoptosis

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

212 1 to form a HIPPI/HIP1 complex that recruits procaspase-8 to begin the process of apoptosis.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

237 IKK1 protein degradation or interaction with procaspase-8.

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

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

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

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

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

243 , which neutralizes Puma and Bim, or loss of procaspase 9 diminished OSI-027-induced apoptosis in vit

244 luding Bcl-2 (an inhibitor of apoptosis) and procaspase-9 (an effector of apoptosis) expression, and

245 tive apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9).

246 caspase-9 activity, since overexpression of procaspase-9 accelerates the rate of apoptosis in active

247 sociation and accelerated the association of procaspase-9 and Apaf-1 in both intact cells and cell-fr

248 , which is responsible for the activation of procaspase-9 and the maintenance of the enzymatic activi

249 rocaspase-3, procaspase-7, procaspase-8, and procaspase-9 and with cleavage of Bid and poly(ADP-ribos

250 y, when implementing the homodimerization of procaspase-9 as a prerequisite for activation, the calcu

251 se-9 sets the overall duration of the timer, procaspase-9 autoprocessing activates the timer, and the

252 apoptosis was inhibited by dominant negative procaspase-9 but not by inhibition of caspase-8 activati

253 m, so that unlike the effector procaspase-3, procaspase-9 cannot be processed by the apoptosome as a

254 e Apaf-1 CARD may be free to interact with a procaspase-9 CARD either before or during apoptosome ass

255 n cells, M1 coimmunoprecipitated with Apaf-1-procaspase-9 complexes.

256 Remarkably, however, procaspase-9 could also bind via its small subunit to th

257 e, we provide the first direct evidence that procaspase-9 homodimerizes within the apoptosome, marked

258 In contrast, assuming a scenario in which procaspase-9 is activated allosterically upon binding to

259 A procaspase-9 mutant (D315A) that cannot produce the p12

260 herein that apoptosome-mediated cleavage of procaspase-9 occurs exclusively through a CARD-displacem

261 ase-3 but had no effect on the processing of procaspase-9 or the activity of prior activated caspase-

262 o its rapid autocatalytic cleavage, however, procaspase-9 per se contributed little to the activation

263 Indeed, procaspase-9 possessed higher affinity for the apoptosom

264 Like cIAP1, XIAP had no effect on procaspase-9 processing and was a more potent inhibitor

265 1 interacts with the apoptosome and prevents procaspase-9 processing as well as downstream procaspase

266 in HeLa cervical cancer cells, half-times of procaspase-9 processing, as well as the molecular timer

267 wed mitochondrial depolarization but blocked procaspase-9 processing, suggesting that M1 targeted the

268 , thereby facilitating a continuous cycle of procaspase-9 recruitment/activation, processing, and rel

269 , wherein the intracellular concentration of procaspase-9 sets the overall duration of the timer, pro

270 Thus, our data suggest that modification of procaspase-9 to protect it from inappropriate cleavage a

271 pression of apoptosome components Apaf-1 and procaspase-9, and limiting caspase-9 activity, since ove

272 s cerevisiae overexpressing human Apaf-1 and procaspase-9, critical components of the apoptosome, or

273 is pathway with purified recombinant Apaf-1, procaspase-9, procaspase-3, and cytochrome c from horse

274 ivation pathway using purified ProT, Apaf-1, procaspase-9, procaspase-3, Hsp70, cytochrome c, PHAPI,

275 en caspase recruitment domains of Apaf-1 and procaspase-9.

276 Procaspase-activating compound 1 (PAC-1) is an o-hydroxy

277 A compound called procaspase-activating compound 1 (PAC-1) was reported th

278 The procaspase-activating compounds (PAC-1), including B-PAC

279 to the development and optimization of other procaspase-activating compounds.

280 These procaspase activators bypass the normal upstream proapop

281 e residues are important for stabilizing the procaspase active site as well as that of the mature cas

282 the loop bundle residues also stabilize the procaspase active site.

283 n specific antibody fragments that stimulate procaspase activity, showing that executioner procaspase

284 tochondrial membrane potential, and enhanced procaspase and poly(ADP-ribose) polymerase cleavage.

285 lly, B-PAC-1 treatment activated executioner procaspases and not other Zn-dependent enzymes.

286 membrane potential and increased cleavage of procaspases and poly(ADP-ribose) polymerase.

287 Significantly, the levels of the procaspases are directly proportional to their activity

288 ough binding to fibrils, which may mimic how procaspases are naturally processed on protein scaffolds

289 ing the residues affects the activity of the procaspase as well as the mature caspase, with D169A and

290 rocaspase activity, showing that executioner procaspase conformational equilibrium can be rationally

291 We hypothesized that direct activation of procaspases could bypass the apoptosis resistance induce

292 on, when coupled to a second mutation in the procaspase, D175A, may alter the substrate specificity o

293 The small-molecule-mediated activation of procaspases has great therapeutic potential and thus thi

294 s negative regulator, Bar, but not the other procaspase molecules.

295 urrently prevailing dogma that all initiator procaspases require homodimerization for activation.

296 ed "death receptor." The identification of a procaspase-specific binding surface on the FADD DED sugg

297 tic cascade is the proteolytic activation of procaspases to active caspases.

298 -PAC-1 (L14R8), convert inactive executioner procaspases to their active cleaved forms by chelation o

299 ular signaling complexes that bring inactive procaspases together and promote their proximity-induced

300 trated that direct activation of executioner procaspases via B-PAC-1 treatment bypasses apoptosis res