ライフサイエンスコーパス: FLICE

1 ase CED-3 (or the mammalian caspases ICE and FLICE).

2 1 and the prodomain of caspase-8 (Mch5/MACH/FLICE).

3 3 (ICE-LAP3, CMH-1), Mch-4, and Mch-5 (MACH, FLICE).

4 cell lines express both FasL and FasR and I-FLICE.

5 activation of a Fas/APO-1-specific protease, FLICE.

6 er, we demonstrate that 14.7K interacts with FLICE.

7 o inhibit apoptosis induced by FADD, but not FLICE.

8 nterleukin-1beta-converting enzyme (ICE) and FLICE.

9 tor directly communicates with FADD and then FLICE.

10 molecules including TRADD, TRAF2, FADD, and FLICE.

11 inhibiting the recruitment and activation of FLICE.

12 scribe the cloning and characterization of I-FLICE, a novel inhibitor of tumor necrosis factor recept

13 of FADD recruitment of FLICE but upstream of FLICE activation by disrupting FADD oligomerization and

14 of additional molecules in Fas signaling and FLICE activation is not clear.

15 : 1) F/F induces cell death, indicating that FLICE activation is sufficient for apoptosis and does no

16 be required for amplification of the initial FLICE activation signal, showed that pro-ICE expression

17 uced apoptosis by interfering with caspase 8/FLICE activation.

18 that CED-4 was required for E1B 19K to block FLICE activation.

19 ins and are important regulators of caspase (FLICE) activity and of apoptosis.

20 changes in expression of FLICE inhibitor (I-FLICE) allow cholangiocarcinoma cells to escape immune s

21 in the death domains is vital for binding to FLICE and for apoptotic activity.

22 of I-FLICE is strikingly similar to that of FLICE and Mch4/FLICE2.

23 tion, did not induce activation of caspase-8/FLICE and neither SPP nor TPA were able to prevent this

24 g FasR signaling through the expression of I-FLICE and/or increased FasL expression to induce apoptos

25 iscovery that the death proteases caspase 8 (FLICE) and caspase 10 (Mch4/FLICE2) are recruited to the

26 pases possessing large and small prodomains (FLICE, and CPP32/YAMA), as well as with the adaptor mole

27 I-FLICE antisense treatment was performed by stable transf

28 rapy also caused a significant activation of FLICE, as evident from the appearance of cleaved product

29 end by a complex that contains U7 snRNP, the FLICE-associated huge protein (FLASH) and histone pre-mR

30 tein, ataxia-telangiectasia locus (NPAT) and FLICE-associated huge protein (FLASH) are two major comp

31 We found that FLICE-associated huge protein (FLASH), which transduces

32 es, and luciferase reporter assay identified FLICE-associated huge protein (FLASH)/caspase-8-associat

33 FLASH (Flice-associated huge protein) and U7 small nuclear RNP

34 f U7 snRNP contains the HLB component FLASH (FLICE-associated huge protein), the histone cleavage com

35 of Mxc, Spt6, and the known HLB components, FLICE-associated huge protein, Mute, U7 small nuclear ri

36 induce cell death, coexpression of CED-4 and FLICE augmented cell death induction by FLICE, which was

37 TNFR-1, FADD (Fas-associated death domain), FLICE, Bad and Bax were ablated in cells expressing PKRd

38 FLICE binds to the death effector domain of FADD and upo

39 cell death downstream of FADD recruitment of FLICE but upstream of FLICE activation by disrupting FAD

40 ppresses the apoptotic pathway downstream of FLICE but upstream of the executioner caspases, caspase-

41 with I-FLICE reduced protein expression of I-FLICE by 90% to 95% and increased Fas-mediated apoptosis

42 ential for the recruitment and activation of FLICE by Fas during the apoptotic signal.

43 The viral FLICE (caspase-8)-like inhibitor proteins (v-FLIPs) are

44 receptor-5), which preferentially engaged a FLICE (caspase-8)-related death protease, was also ident

45 DD-like interleukin-1beta-converting enzyme (FLICE) (caspase-8).

46 through activation of caspase-10, capase-8 (FLICE), caspase-3, and caspase-9.

47 DD-like interleukin-1beta-converting enzyme (FLICE)/caspase-8 in a virus-free system was efficiently

48 D-like interleukin-1-beta-converting enzyme [FLICE/caspase 8]-inhibitory protein (FLIP) activates NF-

49 The activation of FLICE/caspase-8 and CPP32/caspase-3 and cleavage of PARP

50 Caspase-8/10 and FLICE/caspase-8 inhibitory proteins (FLIPs) that inhibit

51 r Fas (CD95)-mediated apoptosis suggest that FLICE/caspase-8 is recruited and activated, which result

52 Western blots showed that FLICE/caspase-8 was upregulated and activated by 24 hour

53 Viral FLIPs (Fas-linked ICE-like protease [FLICE; caspase-8]-like inhibitor proteins) are potent in

54 ore, our results support the hypothesis that FLICE catalyzes a crucial step in the promotion of cell

55 egulated cell survival proteins, including I-FLICE, cIAP-1, cIAP-2, Bcl-2, Bcl-xL, survivin, and X-li

56 whose product is also known as caspase 8 and FLICE, encodes an interleukin-1beta converting enzyme (I

57 Reduction of I-FLICE expression in cholangiocarcinoma cells restored Fa

58 A chimeric Fas/FLICE (F/F) receptor, containing the extracellular/trans

59 ominant negative caspase 9, but not cellular FLICE (FADD-like IL-1b-converting enzyme)-inhibitory pro

60 ion by sustaining the expression of cellular FLICE (FADD-like interleukin-1beta-converting enzyme)-li

61 ns of decoy receptors 1 and 2, Bax, cellular FLICE (Fas-associated death domain protein-like IL-1-con

62 the expression of the antiapoptotic molecule FLICE (Fas-associated death domain-like IL-1-converting

63 FLICE (Fas-associated death domain-like interleukin 1bet

64 diated up-regulation of caspase 8-homologous FLICE (Fas-associated death-domain-like interleukin 1bet

65 he human herpes virus 8 (HHV8)-encoded viral FLICE (Fas-associating protein with death domain-like in

66 cing of the viral cyclin (vcyclin) and viral FLICE (Fas-associating protein with death domain-like in

67 y bind to FADD, nor does it inhibit FADD and FLICE from being recruited to the death-inducing signali

68 y and independently interacts with BclXL and FLICE in mammalian cells.

69 sfection with complementary DNA (cDNA) for I-FLICE in the reverse orientation.

70 Even though E1B 19K did not prevent FLICE-induced apoptosis, it did inhibit CED-4-dependent,

71 Neither viral molecule, however, inhibited FLICE-induced killing, consistent with an inhibitory act

72 of FasR and FasL or changes in expression of FLICE inhibitor (I-FLICE) allow cholangiocarcinoma cells

73 FLICE inhibitory protein (c-FLIP) is an important regula

74 The Fas apoptosis inhibitor molecule and FLICE inhibitory protein (c-FLIP) proteins are up-regula

75 d T cells led to down-regulation of cellular FLICE inhibitory protein (c-FLIP), an inhibitor of apopt

76 aminin, but not collagen, expressed cellular FLICE inhibitory protein (cFLIP) and TNFalpha stimulatio

77 ated death domain (FADD) protein or cellular FLICE inhibitory protein (cFLIP), other proteins associa

78 oarray uncovered down-regulation of cellular FLICE inhibitory protein (cFLIP).

79 ssion of the antiapoptotic molecule cellular FLICE inhibitory protein (cFLIP).

80 short isoform of the caspase-8 inhibitor, c-FLICE inhibitory protein (FLIP(S)), and that FLIP(S) exp

81 ersely related to the intracellular level of FLICE inhibitory protein (FLIP) but not that of death re

82 P, an inhibitor of apoptosis, and disrupting FLICE inhibitory protein (FLIP) expression through the A

83 n of NO and concomitant decrease in cellular FLICE inhibitory protein (FLIP) expression without signi

84 ine, was associated with increased levels of FLICE inhibitory protein (FLIP), and was overcome by cyc

85 ncoding the inhibitor of caspase activation, FLICE inhibitory protein (FLIP), appears to be a direct

86 cies (ROS) generation and down-regulation of FLICE inhibitory protein (FLIP); however, the relationsh

87 ption is regulated by the KSHV-encoded viral FLICE inhibitory protein (vFLIP) and by viral IFN regula

88 -associated herpesvirus (KSHV)-encoded viral FLICE inhibitory protein (vFLIP) enhances IRF4-mediated

89 ines, we have investigated the role of viral FLICE inhibitory protein (vFLIP) in this process.

90 characterized the role of KSHV-encoded viral FLICE inhibitory protein (vFLIP) K13 in the modulation o

91 -associated herpesvirus (KSHV)-encoded viral FLICE inhibitory protein (vFLIP) K13 is a potent activat

92 sarcoma-associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 was originally beli

93 he human herpes virus 8 (HHV8)-encoded viral FLICE inhibitory protein (vFLIP), also known as K13, is

94 Human herpesvirus 8 (HHV-8) encodes a viral FLICE inhibitory protein (vFLIP), called K13, with homol

95 ntly attenuated, but the expression level of FLICE inhibitory protein c-FLIP(L), which had been shown

96 Significantly, the viral flice inhibitory protein E8 protects from p75(NTR)-induc

97 apoptotic effectors such as Bcl-2, p53, and FLICE inhibitory protein in cancer cell anoikis is also

98 -associated herpesvirus (KSHV)-encoded viral FLICE inhibitory protein K13 interacts with a cytosolic

99 ly with the expression of KSHV-encoded viral FLICE inhibitory protein K13.

100 infection or on ectopic expression of viral FLICE inhibitory protein K13.

101 Knockdown of cellular FLICE inhibitory protein potentiates the caspase-depende

102 c-FLIP (cellular FLICE inhibitory protein) is an enzymatically inactive r

103 002 decreases expression of c-FLIP (cellular FLICE inhibitory protein), an inhibitor of caspase-8 act

104 l molecule c-FLIP (cellular homolog of viral FLICE inhibitory protein).

105 lly downregulates expression of the cellular FLICE inhibitory protein, a negative regulator of death

106 riety of anti-apoptotic molecules, including FLICE inhibitory protein, Bcl-2, and Mcl-1, which protec

107 levels of cellular inhibitors of apoptosis (FLICE inhibitory protein, X chromosome-linked inhibitor

108 ellular inhibitor of apoptosis protein-2 and FLICE inhibitory protein.

109 Mature lymphocytes express FLICE inhibitory proteins (FLIPs) that block death recep

110 wn to encode proteins with DEDs (also called FLICE inhibitory proteins or vFLIPs) which have the abil

111 D)-like interleukin-1beta-converting enzyme (FLICE) inhibitory protein (FLIP), leading to apoptosis.

112 e interferon converting enzyme or caspase 8 (FLICE) inhibitory protein (vFLIP) that prevents death re

113 Fas-ligand interleukin-1-converting enzyme (FLICE)-inhibitory protein (c-FLIP), an endogenous antago

114 rleukin 1 beta (IL-1beta)-converting enzyme (FLICE)-inhibitory protein (FLIP) has been reported to in

115 Cellular FLICE-inhibitory protein (c-FLIP(L)) is a key regulator

116 receptor, and reduces the levels of cellular FLICE-inhibitory protein (c-FLIP) (both the long and sho

117 ib down-regulated the expression of cellular FLICE-inhibitory protein (c-FLIP), a major negative regu

118 oxib action based on degradation of cellular FLICE-inhibitory protein (c-FLIP), a major regulator of

119 Cellular FLICE-inhibitory protein (c-FLIP), an antioxidant and an

120 MRIT, also known as c-FLICE-inhibitory protein (c-FLIP), is an enzymatically i

121 s was associated with a decrease in cellular FLICE-inhibitory protein (c-FLIP).

122 uced the mRNA and protein levels of cellular FLICE-inhibitory protein (c-FLIP).

123 companied by the down-regulation of cellular FLICE-inhibitory protein (c-FLIP, I-FLICE) without evide

124 ible or permanent) with deletion of cellular FLICE-inhibitory protein (cFlip) or caspase-8 in the int

125 coy receptors and the antiapoptotic cellular FLICE-inhibitory protein (cFLIP) was inconsistent across

126 ell leukemia-1 (Mcl-1) and caspase 8 homolog FLICE-inhibitory protein (cFLIP), and induced G2M cell-c

127 ysis showed higher transcript levels for the FLICE-inhibitory protein (FLIP(L)) in resistant cells an

128 ates the degradation of the long form of the FLICE-inhibitory protein (FLIP(L)), an inhibitor of deat

129 FLICE-inhibitory protein (FLIP) blocks death receptor-me

130 Levels of DcR1 and DcR2 or levels of the FLICE-inhibitory protein (FLIP) did not correlate with T

131 The caspase-8 homologue FLICE-inhibitory protein (FLIP) functions as a caspase-8

132 FLICE-inhibitory protein (FLIP) is a homolog of caspase-

133 FLICE-inhibitory protein (FLIP), an inhibitor of Fas act

134 ndent and correlated with down-regulation of FLICE-inhibitory protein (FLIP), an intracellular caspas

135 for various apoptosis inhibitors, including FLICE-inhibitory protein (FLIP), and lower procaspase-8

136 decoy recepter 2) or antiapoptotic proteins (FLICE-inhibitory protein (FLIP), inhibitor of apoptosis

137 proliferation when the caspase 8 inhibitor, FLICE-inhibitory protein (FLIP), is active.

138 Expression of one such inhibitor, FLICE-inhibitory protein (FLIP), was highest in the TRAI

139 ibited expression of the caspase-8 inhibitor FLICE-inhibitory protein (FLIP), which functions downstr

140 ity correlated with a progressive decline in Flice-inhibitory protein (FLIP), which was induced withi

141 Here, we have revealed the role of viral FLICE-inhibitory protein (vFLIP) in the initiation of PE

142 HHV8 encodes for a viral FLICE-inhibitory protein (vFLIP), designated K13, which

143 ation of B lymphocytes by KSHV-encoded viral FLICE-inhibitory protein (vFLIP).

144 pression of the antiapoptotic genes cellular FLICE-inhibitory protein and Bcl-2.

145 ll death and caspase activation by promoting FLICE-inhibitory protein degradation and mitochondrial r

146 own that the antiapoptotic molecule cellular-FLICE-inhibitory protein long isoform [c-FLIP(L)] is nec

147 R4/TRAIL R1, Fas-associated death domain and FLICE-inhibitory protein proteins.

148 sociated herpesvirus (KSHV) K13/vFLIP (viral Flice-inhibitory protein) induces transcription of numer

149 were attenuated by the forced expression of FLICE-inhibitory protein.

150 FLICE-inhibitory proteins (FLIPs) are a family of viral

151 (KSHV) genomes encode a homolog of cellular FLICE-inhibitory proteins (termed v-FLIP) that activates

152 rotein that is homologous to cellular FLIPs (FLICE-inhibitory proteins) and is proposed to inhibit Fa

153 , inhibitor of apoptosis proteins, and viral FLICE-inhibitory proteins.

154 Viral flice-interacting protein (vFLIP), encoded by the oncoge

155 These results support the idea that FLICE is a cellular target for the 14.7-kDa protein.

156 , or LAP3 in vivo but that its inhibition of FLICE is of a magnitude for this protease to be a key ta

157 ase in the death receptor pathway, caspase-8/FLICE is rapidly down-regulated at the mRNA level repres

158 The overall architecture of I-FLICE is strikingly similar to that of FLICE and Mch4/FL

159 I-FLICE is the first example of a catalytically inert casp

160 ptor associated cysteine protease Mch5 (MACH/FLICE) is believed to be the enzyme responsible for acti

161 ction of this molecule is similar to that of FLICE, it has been designated FLICE2.

162 nzyme and the second highest for the caspase FLICE (Ki = 0.95 nM), identified as a component of the i

163 However, I-FLICE lacks both a catalytic active site and residues th

164 death receptor inhibitor cellular caspase 8 (FLICE)-like inhibitory protein (c-FLIP) is required for

165 ous studies suggest that cellular caspase 8 (FLICE)-like inhibitory protein (c-FLIP) promotes cell su

166 DD-like interleukin-1beta-converting enzyme (FLICE)-like inhibitory protein (FLIP), and reduced FLIP

167 totic proteins cFLIP(L) (cellular caspase-8 (FLICE)-like inhibitory protein), Bcl-2, and Bcl-X(L) and

168 r was mediated in part by the stimulation of FLICE-like inhibiting protein expression, the attenuatio

169 ix peptide, which was derived from the viral FLICE-like inhibitor protein (vFLIP) of Kaposi's sarcoma

170 with Akt-mediated stabilization of cellular FLICE-like inhibitory protein (c-FLIP) and Mcl-1.

171 lly deleting the antiapoptotic gene cellular FLICE-like inhibitory protein (C-FLIP) in myeloid cells,

172 ion of the FAS-mediated apoptosis pathway by FLICE-like inhibitory protein (c-FLIP) may contribute to

173 Here we show a novel mechanism by which FLICE-like inhibitory protein (c-FLIP) regulates apoptos

174 duced apoptosis was associated with cellular FLICE-like inhibitory protein (c-FLIP) turnover and that

175 We show that cellular FLICE-like inhibitory protein (c-FLIP), a procaspase-8-l

176 Three of the genes, RelA, cellular FLICE-like inhibitory protein (c-FLIP), and a dominant-n

177 tination of the caspase-8 regulator cellular FLICE-like inhibitory protein (c-FLIP), targeting it for

178 Overexpression of cellular FLICE-like inhibitory protein (c-FLIP-s) or knockdown of

179 ckdown of CD95 or overexpression of cellular FLICE-like inhibitory protein (c-FLIP-s).

180 Overexpression of cellular FLICE-like inhibitory protein (cFLIP) is reported to con

181 The cellular FLICE-like inhibitory protein (cFLIP) is reported to inh

182 Cellular FLICE-like inhibitory protein (cFLIP) overexpression and

183 tic (TRAIL-R3, TRAIL-R4) receptors, cellular FLICE-like inhibitory protein (cFLIP), caspase-3 and cas

184 showed that WEHI-231 expressed an isoform of FLICE-like inhibitory protein (cFLIPL), an antiapoptotic

185 min B, and down-regulated cellular levels of FLICE-like inhibitory protein (FLIP) and X-chromosome-li

186 The viral FLICE-like inhibitory protein (FLIP) protein from Kaposi

187 exposure resulted in decreased expression of FLICE-like inhibitory protein (FLIP), an anti-apoptotic

188 rosurvival in the presence of CDDP through a FLICE-like inhibitory protein (FLIP)-Itch interaction.

189 hich correlates with decreased expression of FLICE-like inhibitory protein (FLIP).

190 tected viral interleukin-6 (vIL-6) and viral FLICE-like inhibitory protein (vFLIP) transcripts.

191 receptors as well as expression of cellular FLICE-like inhibitory protein and caspase-2, -3, -8, -9,

192 MC38-FasL/FLICE-like inhibitory protein colon cancer cells induce

193 Expression of FLICE-like inhibitory protein confers apoptosis resistan

194 ing in a proteolytically active complex with FLICE-like inhibitory protein long (FLIP(L), also known

195 tein with death domain), or c-FLIP (cellular FLICE-like inhibitory protein) expression.

196 Cellular FLIP (Flice-like inhibitory protein) is critical for the prote

197 ses the steady state protein levels of FLIP (FLICE-like inhibitory protein), an inhibitor of the Fas

198 ligand, death receptor 5, decoy receptor 2, FLICE-like inhibitory protein, signal transducers and ac

199 Expression of cellular FLICE-like inhibitory protein-short did not significantl

200 ic protease activating factor-1, or cellular FLICE-like inhibitory protein.

201 NA expression of TRAIL receptors or cellular FLICE-like inhibitory protein.

202 ted phosphorylation of AKT and activation of FLICE-like-inhibitory-protein (FLIP).

203 that possesses overall sequence homology to FLICE (MACH), a large prodomain caspase that links the a

204 (FADD) interleukin-1beta-converting enzyme (FLICE)/MACH was recruited to the CD95 signaling complex

205 ERICE, however, was activated by caspase-8 (FLICE, MACH, Mch-5), the apical caspase activated upon e

206 Therefore, FLICE/MACH represents the apical triggering protease in

207 an increase in expression of pro-caspase-8 (FLICE/MACH) but does not significantly change expression

208 member of the caspase family, a homologue of FLICE/MACH, and Mch4.

209 a novel ICE/CED-3 family member, designated FLICE/MACH, to the receptor signaling complex.

210 ymogen form of the death protease caspase-8 (FLICE/Mach-1) by a homophilic interaction involving the

211 sis mediated by CD95 (Fas/APO-1), caspase-8 (FLICE/MACH/Mch5) is immediately activated and, in princi

212 death domain protein (FADD), and caspase-8 (FLICE/MACH/Mch5).

213 teract with the cysteine protease caspase-8 (FLICE/MACH/Mch5).

214 apeutic maneuvers to inhibit expression of I-FLICE may aid in the treatment of cholangiocarcinoma.

215 DD-like interleukin-1beta converting enzyme (FLICE)-mediated processing of caspase-3/CPP32.

216 ane portion of Fas and the caspase region of FLICE, mediated anti-Fas apoptosis.

217 d apoptosis, it did inhibit CED-4-dependent, FLICE-mediated apoptosis, which suggested that CED-4 was

218 FADD then activates caspase 8 (also known as FLICE or MACH) through an interaction between the death-

219 FADD and FLICE participate in generating the death signal from bo

220 CAP3 was identified as the FLICE prodomain which likely remains bound to the recept

221 FLICE protease subunits were generated from the F/F prec

222 oximal defects in Fas signaling that prevent FLICE recruitment or activation.

223 tment of cholangiocarcinomas in vitro with I-FLICE reduced protein expression of I-FLICE by 90% to 95

224 However, since FLICE represents the most apical caspase in the Fas path

225 creation of a nonprocessable zymogen form of FLICE that retained low but detectable protease activity

226 However, unlike FLICE, the C-terminal domain of MRIT lacks the caspase c

227 induced cell death attenuates the ability of FLICE to activate downstream caspases.

228 ted FADD filament formation causing FADD and FLICE to relocalize to membrane and cytoskeletal structu

229 DD-like interleukin-1beta-converting enzyme (FLICE), to induce an apoptotic response.

230 Consistent with this, recombinant FLICE was found capable of proteolytically activating do

231 brogated by E1B 19K and Bcl-xL when FADD and FLICE were coexpressed.

232 ated death domain protein (TRADD) to FADD to FLICE, whereas for CD-95 the receptor directly communica

233 4 encodes a novel 55 kDa protein, designated FLICE, which has homology to both FADD and the ICE/CED-3

234 and FLICE augmented cell death induction by FLICE, which was blocked by expression of E1B 19K.

235 cellular FLICE-inhibitory protein (c-FLIP, I-FLICE) without evidence of Fas (CD95) up-regulation.

236 ly after recruitment, the single polypeptide FLICE zymogen is proteolytically processed to the active

237 We hypothesized that the FLICE zymogen possesses intrinsic enzymatic activity suc