ライフサイエンスコーパス: FLIP

1 FLIP (Fas-associated via death domain-like interleukin 1

2 FLIP is a well-established suppressor of death receptor-

3 FLIP studies also showed that mitochondria that enter th

4 FLIP(L) depletion also modulated transcription of canoni

5 FLIP(S) half-life in PTEN mutant GBM cells was reduced b

6 FLIPs are a family of viral and cellular proteins initia

7 Thus, even in the absence of caspase-8/10, FLIP(L) silencing promoted p53-induced apoptosis by enha

8 regulation is postulated, but exactly how a FLIP performs such multifunctional roles remains to be e

9 Moreover, silencing of Cbl abrogated FLIP(S) reduction induced by rictor knockdown.

10 , an event previously shown to increase AIP4-FLIP(S) interaction, whereas siRNA-mediated suppression

11 vate antiapoptotic genes, including BCL2 and FLIP.

12 Caspase-8, FADD, and FLIP orchestrate apoptosis in response to death receptor

13 the mechanism by which caspase-8, FADD, and FLIP prevent runaway RIPK activation is unknown, and the

14 the lethal defect in caspase-8-, FADD-, and FLIP-deficient animals and tissues.

15 In macrophages, FLIP long (FLIP(L)) and FLIP short (FLIP(S)) mRNA was induced by tumor necrosis

16 termine whether the use of the SAF score and FLIP algorithm can decrease interobserver variations amo

17 n Group 2 after the use of the SAF score and FLIP algorithm.

18 Survivin and FLIP anti-apoptotic factors, vascular endothelial growth

19 c-FLIP silencing with anti-FLIP short interfering RNA (siRNA) in pulmonary MVECs re

20 TRAIL, and antiapoptotic molecules, such as FLIP and Bcl-xL, in inflammatory cells from thyroids of

21 kappaB p65 and NFkappaB inhibitor attenuated FLIP protein levels in SCC cells.

22 ells, were not sensitized to these agents by FLIP silencing.

23 It is negatively regulated by FLIP, cIAP1, cIAP2, and XIAP.

24 c-FLIP can inhibit death receptor-mediated apoptosis by co

25 c-FLIP may inhibit or promote T cell death as previous dat

26 c-FLIP protein levels are regulated by ubiquitination and

27 c-FLIP silencing with anti-FLIP short interfering RNA (siR

28 c-FLIP(f/f) LysM-Cre mice exhibit delayed clearance of cir

29 Although c-FLIP has been identified as an important player in the e

30 e1 expressed increased levels of Bcl-2 and c-FLIP and decreased levels of Fas RNA compared with HKIR

31 positive cross-talk exists between Akt and c-FLIP in the context of inhibition of FasL-induced NF-kap

32 ted antiapoptotic genes bfl-1, cIAP-2, and c-FLIP.

33 re differentially regulated by cIAP1/2 and c-FLIP.

34 ase inhibitors was sufficient to attenuate c-FLIP levels.

35 and that gamma-secretase inhibitor blocked c-FLIP turnover and also partially blocked PS1-induced apo

36 assembly and activation are controlled by c-FLIP isoforms, which function as pro-apoptotic (c-FLIPL

37 /TRAIL can be restored at least in part by c-FLIP pathway inhibitors.

38 e granulocytic subset, requires continuous c-FLIP expression to prevent caspase-8-dependent, RIPK3-in

39 We found that celecoxib controlled c-FLIP ubiquitination through Akt-independent inhibition o

40 itiator caspase activation and cell death, c-FLIP(L) is also capable of enhancing procaspase-8 activa

41 s of other related proteins including DR4, c-FLIP, FADD, and caspase-8.

42 onstrate that acute deletion of endogenous c-FLIP in murine effector T cells results in loss of caspa

43 -8 activation is not blocked by endogenous c-FLIP.

44 een NF-kappaB and PI3K/Akt and establishes c-FLIP as an important regulator of FasL-mediated cell dea

45 lf, were viable, as were mice that express c-FLIP or CYLD proteins that had been mutated to prevent c

46 ing CD95 expression or in cells expressing c-FLIP-s, the lethality of sorafenib + HDACI exposure was

47 d by a complex comprising caspase-8, FADD, c-FLIP, and a kinase-dependent function of RIPK1.

48 lthough the long isoform of cellular FLIP (c-FLIP(L)) has been implicated in TCR-mediated signaling,

49 ing enzyme inhibitory protein, short form (c-FLIP-s) blocked enhanced killing.

50 sion of endogenous NF-kappaB target genes (c-FLIP, TRAF1), and resistance to apoptosis.

51 role of c-FLIPL and crucially defines how c-FLIP isoforms differentially control cell fate.

52 xygen species (ROS) has been implicated in c-FLIP protein degradation.

53 or increase in reactive oxygen species in c-FLIP-deficient resting T cells.

54 deletion rescued the enhanced apoptosis in c-FLIP-deficient T cells, whereas inhibition of caspase 8

55 ed apoptosis in association with increased c-FLIP levels.

56 e effects of GSK3 inhibition and increased c-FLIP ubiquitination, confirming that c-FLIP attenuation

57 pletion of TRAF7 correlates with increased c-FLIP(L) expression level, which, in turn, results in res

58 ated with the intrinsic apoptosis inducer, c-FLIP suppressed cytochrome c release from mitochondria.

59 repression of cellular caspase-8 inhibitor c-FLIP (also known as CFLAR) expression through activation

60 liminating endogenous caspase-8 inhibitor, c-FLIP, while Smac mimetic does so by triggering autodegra

61 Thus, not only is c-FLIP the initiator of caspase-8 activity during T cell a

62 knockout mouse strain specifically lacking c-FLIP(L) in T lymphocytes.

63 ne sulfoximine down-regulates c-FLIP long (c-FLIP(L)) protein levels, which is prevented by the prote

64 n were found to be important for mediating c-FLIP-dependent downregulation of NF-kappaB activity.

65 rthermore, the expression of Mcl-1 but not c-FLIP was significantly reduced when COX-2 was suppressed

66 reduced the abundance of the short form of c-FLIP (FLIP(S), CFLAR(S)) and survivin (BIRC5).

67 th GSK3 inhibition enhanced attenuation of c-FLIP and increased apoptosis.

68 atment resulted in decreased expression of c-FLIP and Mcl-1, which were determined to be transcriptio

69 presence of two death effector domains of c-FLIP and S-nitrosylation of its caspase-like domain were

70 -dependent pathway mediated by turnover of c-FLIP and the gamma-secretase-independent pathway mediate

71 this protein in regulating the turnover of c-FLIP and, consequently, cell death.

72 mediated apoptosis, while up-regulation of c-FLIP by gene transfer partially protected dermal MVECs f

73 Inhibition of c-FLIP by means of RNA interference increased Apo2/TRAIL s

74 o involve cytokine-induced acceleration of c-FLIP degradation, sensitizing cells to TRAIL-mediated ca

75 not Treg cells because of higher levels of c-FLIP expression in Treg cells.

76 To investigate the function of c-FLIP in mature T cells, we have generated several geneti

77 sm through which the regulatory effects of c-FLIP on death receptor signaling are controlled by GSK3,

78 ion of NF-kappaB through overexpression of c-FLIP or IKK (also known as CFLAR and IKBKB, respectively

79 Short hairpin RNA-mediated knockdown of c-FLIP or Mcl-1 significantly sensitized these cells to TR

80 re T lymphocytes in vitro, and the role of c-FLIP protein in intrinsic apoptosis pathway was studied.

81 Accordingly, expression of c-FLIP T166A or K167R mutants protected cells from ROS-med

82 Moreover, down-regulation of c-FLIP using small interfering RNA in nonactivated T cells

83 structures of the protease-like domain of c-FLIP(L) alone and in complex with zymogen C8 identify th

84 LIP(L) and demonstrate that degradation of c-FLIP(L) also occurs through a lysosomal pathway.

85 hat cleavage of the intersubunit linker of c-FLIP(L) by procaspase-8 potentiates the activation proce

86 de molecular insights into a key aspect of c-FLIP(L) function that modulates procaspase-8 activation

87 sine 167 as a novel ubiquitination site of c-FLIP(L) important for ROS-dependent degradation.

88 To establish the role of c-FLIP(L) in T lymphocyte proliferation, we have generated

89 s have demonstrated that overexpression of c-FLIP(L) promotes T cell proliferation and NF-kappaB acti

90 enger prevented ubiquitination and loss of c-FLIP(L) protein induced by menadione or paraquat.

91 ATL by transcriptional down-regulation of c-FLIP, a key inhibitor of death receptor signaling, and b

92 ity in association with down-regulation of c-FLIP, suggesting that c-FLIP synthesis, not intracellula

93 this may be mediated by down-regulation of c-FLIP.

94 ectin, soluble factor(s) have no impact on c-FLIP redistribution within cellular compartments.

95 substrate repertoire, limited to itself or c-FLIP.

96 The caspase-8 paralogue c-FLIP is a good candidate for a molecular rheostat of cas

97 that fail to activate caspase-8 and permit c-FLIP(L) cleavage cannot facilitate NF-kappaB activation

98 The cytosolic protein c-FLIP (cellular Fas-associated death domain-like interleu

99 eline levels of the anti-apoptotic protein c-FLIP in all cell lines tested.

100 Cellular FLICE-inhibitory protein (c-FLIP(L)) is a key regulator of the extrinsic cell death

101 of cellular FLICE-like inhibitory protein (c-FLIP) and Mcl-1.

102 optosis regulator-like inhibitory protein (c-FLIP) and myeloid cell leukemia 1 (Mcl-1).

103 ne cellular FLICE-like inhibitory protein (C-FLIP) in myeloid cells, we have generated a novel mouse

104 caspase 8 (FLICE)-like inhibitory protein (c-FLIP) is required for TNFalpha-induced protection agains

105 caspase 8 (FLICE)-like inhibitory protein (c-FLIP) promotes cell survival in death receptor-induced a

106 th cellular FLICE-like inhibitory protein (c-FLIP) turnover and that gamma-secretase inhibitor blocke

107 tion of cellular FLICE-inhibitory protein (c-FLIP), a major regulator of the death receptor pathway o

108 Cellular FLICE-inhibitory protein (c-FLIP), an antioxidant and an important component of the

109 tion of cellular FLICE inhibitory protein (c-FLIP), an inhibitor of apoptosis.

110 or cellular FLICE-like inhibitory protein (c-FLIP), targeting it for proteasome degradation.

111 ease in cellular FLICE-inhibitory protein (c-FLIP).

112 of cellular FLICE-like inhibitory protein (c-FLIP-s) or knockdown of CD95 suppressed the lethality of

113 of cellular FLICE-like inhibitory protein (c-FLIP-s).

114 iquitination of the anti-apoptotic protein c-FLIP(L) and demonstrate that degradation of c-FLIP(L) al

115 pases-8 and -10 and the regulatory protein c-FLIP.

116 APL cells, in which PMLRARalpha recruited c-FLIP(L/S) and excluded procaspase 8 from Fas death signa

117 use TGM2 suppression significantly reduced c-FLIP but not Mcl-1 expression.

118 ent caused DISC formation without reducing c-FLIP-s expression and did not increase CD95 plasma membr

119 which ROS post-transcriptionally regulate c-FLIP protein levels is not well understood.

120 ssential for soluble factor(s) to regulate c-FLIP.

121 , or buthionine sulfoximine down-regulates c-FLIP long (c-FLIP(L)) protein levels, which is prevented

122 166 or Lys-167 was sufficient to stabilize c-FLIP protein levels in PPC-1, HEK293T, and HeLa cancer c

123 In this study, c-FLIP gene was deleted in mature T lymphocytes in vitro,

124 ng therapeutic potential, act by targeting c-FLIP ubiquitination and degradation by the proteasome.

125 sed c-FLIP ubiquitination, confirming that c-FLIP attenuation was mediated by proteasomal turnover as

126 Current models assume that c-FLIP directly competes with procaspase-8 for recruitment

127 These data suggest that c-FLIP is a negative regulator of intrinsic apoptosis path

128 Surprisingly, we found that c-FLIP protects mature T cells not only from apoptosis ind

129 down-regulation of c-FLIP, suggesting that c-FLIP synthesis, not intracellular traffic, is essential

130 These results demonstrate that c-FLIP(L) is essential for T lymphocyte proliferation thro

131 ivation, whereas others have reported that c-FLIP(L) overexpression has no effect or even inhibits T

132 nt post-translational modifications of the c-FLIP protein that regulate its stability, thus impacting

133 eath as previous data demonstrate that the c-FLIP(L) isoform can promote or inhibit caspase 8 activat

134 Although the c-FLIP(R) isoform inhibits cell death in cell lines, its f

135 or inhibit caspase 8 activation while the c-FLIP(S) isoform promotes or inhibits T cell death when o

136 ediated TRAIL resistance is likely through c-FLIP because TGM2 suppression significantly reduced c-FL

137 Thus, c-FLIP plays an essential role in protecting mature T cell

138 not alter the activity of caspase-8 toward c-FLIP(L), which is required for antigenic signaling.

139 Whether c-FLIP regulates mitochondrion-dependent apoptotic signals

140 enerated several genetic mouse models with c-FLIP or its individual isoforms deleted in mature T cell

141 rming an apoptotic inhibitory complex with c-FLIP.

142 Total levels of the candidate FLIP(S) E3 ubiquitin ligase atrophin-interacting protein

143 ase-8 paralog and only human pseudo-caspase, FLIP(L), in regulating this switch.

144 However, CD2-FLIP Tg(+) donors often transferred less severe G-EAT, e

145 Cellular FLIP (cFLIP) forms are also known to activate the NF-kap

146 Cellular FLIP (cFLIP) is a homolog of caspase 8 and is also capab

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

148 els of the Fas-signaling antagonist cellular FLIP (cFLIP) in germinal center (GC) B cells suggests an

149 Although the long isoform of cellular FLIP (c-FLIP(L)) has been implicated in TCR-mediated sig

150 tor of apoptosis protein (cpIAP) or cellular FLIP (FLICE-like inhibitory protein) gene restored the W

151 The cellular FLIP long isoform protein (cFLIPL) controls type I IFN p

152 kt, regulates the ability of AIP4 to control FLIP(S) stability and TRAIL sensitivity.

153 IP(S) ubiquitination, USP8 seemed to control FLIP(S) ubiquitination through an intermediate target.

154 Here, we present CRISPR-FLIP, a strategy that provides an efficient, rapid and s

155 on of AIP4 levels in PTEN WT cells decreased FLIP(S) ubiquitination, prolonged FLIP(S) half-life, and

156 Rictor knockdown decreased FLIP(S) stability, whereas enforced expression of rictor

157 tion, decreased FLIP(S) half-life, decreased FLIP(S) steady-state levels, and decreased TRAIL resista

158 PP242 decreased FLIP(S) stability, increased FLIP(S) ubiquitination, and

159 increased FLIP(S) ubiquitination, decreased FLIP(S) half-life, decreased FLIP(S) steady-state levels

160 s longer half-life correlated with decreased FLIP(S) polyubiquitination.

161 but not raptor, mimicked PP242 in decreasing FLIP(S) levels and sensitizing cells to TRAIL.

162 3 mutation/inflammasome activation-dependent FLIP addiction, co-occurring KRAS and LKB1 mutation-driv

163 ble form of FOXO3a (FOXO3aTM), downregulates FLIP protein and mRNA.

164 Enforced expression of ectopic FLIP(S), but not survivin, attenuated augmented apoptosi

165 DR5) and its downstream regulators/effectors FLIP, Caspase-8, and FADD had particularly poor prognose

166 etylase 1 (HDAC1) or HDAC3 on the endogenous FLIP promoter but not in mice lacking p50.

167 uitment, the FADD DED preferentially engages FLIP using its alpha1/alpha4 surface and procaspase 8 us

168 Moreover, TNFalpha enhanced FLIP(L) serine phosphorylation, which was increased by a

169 Here we examine FLIPs (MC159 and MC160) encoded by the molluscum contagi

170 (59 of 60) of human STS specimens exhibited FLIP expression, suggesting that the nuclear IRF8 protei

171 ased FLIP(S) ubiquitination, and facilitated FLIP(S) degradation.

172 The DEDs of FADD, FLIP and procaspase 8 interact with one another using tw

173 d the abundance of the short form of c-FLIP (FLIP(S), CFLAR(S)) and survivin (BIRC5).

174 We show herein that ROS are required for FLIP down-regulation and apoptosis induction by Fas liga

175 a primary oxidative species responsible for FLIP down-regulation, whereas superoxide serves as a sou

176 expected, therapeutically relevant roles for FLIP(L) in determining cell fate following p53 activatio

177 activity, identifying a unique function for FLIPs.

178 As such, a broad role for FLIPs in disease regulation is postulated, but exactly h

179 ata were exported to software that generated FLIP topography plots.

180 pressed and CDDP failed to abolish the I-GSN-FLIP-Itch interaction, resulting in the dysregulation of

181 sistance in cancer cells by altering the GSN-FLIP-Itch interaction.

182 Application of HiTS-FLIP to the protein Gcn4 (Gcn4p), the master regulator o

183 orescent ligand interaction profiling' (HiTS-FLIP), a technique for measuring quantitative protein-DN

184 Moreover, we identify FLIP(L) as a direct p53 transcriptional target gene that

185 We hypothesized that if FLIP were overexpressed on lymphocytes, CD4(+) effector

186 ent disease, G-EAT resolution was delayed in FLIP transgenic mice.

187 that it is mTORC2 inhibition that results in FLIP(S) downregulation and subsequent sensitization of T

188 73, a putative Akt-1 phosphorylation site in FLIP(L), was critical for the activation-induced reducti

189 from IRF8-null mice also exhibited increased FLIP protein level, suggesting that IRF8 might be a gene

190 PP242 decreased FLIP(S) stability, increased FLIP(S) ubiquitination, and facilitated FLIP(S) degradat

191 g expression of FOXO3aTM, leads to increased FLIP expression.

192 but increased AIP4 ubiquitination, increased FLIP(S) steady-state levels, and suppressed FLIP(S) ubiq

193 t not catalytically inactive USP8, increased FLIP(S) ubiquitination, decreased FLIP(S) half-life, dec

194 rupting IRF8 function dramatically increases FLIP mRNA stability, resulting in increased IRF8 protein

195 E3 ligase Cbl (CBL) abolished PP242-induced FLIP(S) reduction.

196 by CDDP in sensitive cells, thereby inducing FLIP ubiquitination and degradation, followed by apoptos

197 ded with agents that downregulate or inhibit FLIP are promising candidate agents for the treatment of

198 d superoxide dismutase effectively inhibited FLIP down-regulation and apoptosis induction by FasL.

199 s the DEDs of procaspase 8 and its inhibitor FLIP to form death-inducing signalling complexes (DISCs)

200 Thus, it is FLIP(S) downregulation that contributes to synergistic i

201 In macrophages, FLIP long (FLIP(L)) and FLIP short (FLIP(S)) mRNA was induced by tu

202 lex with FLICE-like inhibitory protein long (FLIP(L), also known as CFLAR), and this complex is requi

203 In macrophages, FLIP long (FLIP(L)) and FLIP short (FLIP(S)) mRNA was in

204 Mechanistically, FLIP(L) inhibited p53-induced apoptosis by blocking acti

205 ogether, our data suggest that IRF8 mediates FLIP expression level to regulate apoptosis and targetin

206 educed the protein level of FLIP(L), but not FLIP(S), at 1 and 2 h.

207 ith Tg(-) littermates, presumably because of FLIP overexpression on B cells.

208 complex and the degradation and cleavage of FLIP, an inhibitor of caspase-8, in renal cystic epithel

209 -disk confocal imaging with a combination of FLIP, FRAP, and photoactivatable GFP-Bax, we demonstrate

210 , PP242 induces Cbl-dependent degradation of FLIP(S), leading to FLIP(S) downregulation.

211 r pharmacologically inhibiting expression of FLIP(L) using siRNA or entinostat (a clinically relevant

212 served TNFalpha reduced the protein level of FLIP(L), but not FLIP(S), at 1 and 2 h.

213 eubiquitinase correlated with high levels of FLIP(S) ubiquitination, USP8 seemed to control FLIP(S) u

214 Transgenic overexpression of FLIP protected cultured splenocytes from Fas-mediated, b

215 poptosis due to transgenic overexpression of FLIP.

216 t TNF was protective only in the presence of FLIP(L).

217 The reduction of FLIP(L) by TNFalpha was not mediated by caspase 8, or th

218 ere by TNFalpha facilitates the reduction of FLIP(L) protein, which is dependent on the phosphatidyli

219 The reduction of FLIP(L) resulted in the short term induction of caspase

220 ical for the activation-induced reduction of FLIP(L).

221 ROS mediate the down-regulation of FLIP by ubiquitination and subsequent degradation by pro

222 USP8 links Akt to AIP4 and the regulation of FLIP(S) stability and TRAIL resistance.

223 PTEN-Akt-AIP4 pathway as a key regulator of FLIP(S) ubiquitination, FLIP(S) stability, and TRAIL sen

224 ng that IRF8 might be a general repressor of FLIP.

225 Deletion of JNK led to the stabilization of FLIP L, reduced caspase-8 activation, decreased Bid clea

226 Furthermore, the suppression of FLIP(S) levels by USP8 overexpression was reversed by th

227 en interact via the alpha1/alpha4 surface of FLIP DED1 and the alpha2/alpha5 surface of procaspase 8

228 eal previously unappreciated complexities of FLIPs, and that subtle differences within the conserved

229 differences within the conserved regions of FLIPs possess distinct molecular and structural fingerpr

230 The comparative study of FLIPs provides a unique basis to understand virus-host i

231 combined effects of androgens and FOXO3a on FLIP transcription.

232 rescue was diminished when either FOXO3a or FLIP was reduced by siRNA.

233 enerated transgenic (Tg) mice overexpressing FLIP under the CD2 promoter.

234 Similarly, cFLIPSand p22-FLIP also require TAK1 but do not require LUBAC.

235 L, cFLIPS, and their proteolytic product p22-FLIP all require the C-terminal region of NEMO/IKKgamma

236 Fluorescence loss in photobleaching (FLIP) and network analysis experiments revealed that mit

237 Fluorescence loss in photobleaching (FLIP) reveals constant retrotranslocation of WT Bax, but

238 The functional lumen imaging probe (FLIP) could improve the characterization of achalasia su

239 ithm (fatty liver inhibition of progression [FLIP]) for the classification of liver injury in morbid

240 decreased FLIP(S) ubiquitination, prolonged FLIP(S) half-life, and increased TRAIL resistance.

241 The antiapoptotic protein FLIP(S) is a key suppressor of tumor necrosis factor-rel

242 ncreases levels of the antiapoptotic protein FLIP(S), and confers resistance to tumor necrosis factor

243 FLICE-inhibitory protein (FLIP) blocks death receptor-mediated apoptosis by inhibi

244 The viral FLICE-like inhibitory protein (FLIP) protein from Kaposi sarcoma-associated herpesvirus

245 ting enzyme (FLICE)-like inhibitory protein (FLIP), and reduced FLIP expression precedes apoptosis af

246 DDP through a FLICE-like inhibitory protein (FLIP)-Itch interaction.

247 down-regulation of FLICE inhibitory protein (FLIP); however, the relationship between these two event

248 ced expression of the antiapoptotic proteins FLIP, Mcl-1, Bcl-2, cIAP1, cIAP2, and survivin.

249 FLICE-inhibitory proteins (FLIPs) are a family of viral (poxvirus and herpesvirus)

250 Reduced FLIP levels correlated with reductions in phosphorylated

251 -like inhibitory protein (FLIP), and reduced FLIP expression precedes apoptosis after androgen withdr

252 ts, while in LNCaP cells, androgens regulate FLIP in a manner that is dependent on phosphoinositol-3-

253 inhibitor camptothecin (CPT) down-regulated FLIP in pancreatic cancer models and enhanced apoptosis

254 teracting protein 4 (AIP4) pathway regulates FLIP(S) ubiquitination and stability, although the means

255 scavenger of NO, which positively regulates FLIP via S-nitrosylation.

256 alphaDR5-NPs was enhanced by down-regulating FLIP, a key modulator of death receptor-mediated activat

257 ophages, FLIP long (FLIP(L)) and FLIP short (FLIP(S)) mRNA was induced by tumor necrosis factor (TNF)

258 Silencing FLIP expression significantly increased human sarcoma ce

259 These results indicate that silencing FLIP does not necessarily bypass the requirement for mit

260 on; therefore, we assessed whether silencing FLIP could convert type II cells into type I.

261 eas enforced expression of rictor stabilized FLIP(S).

262 irst evidence showing that mTORC2 stabilizes FLIP(S), hence connecting mTORC2 signaling to the regula

263 FLIP(S) steady-state levels, and suppressed FLIP(S) ubiquitination.

264 Furthermore, targeting FLIP and XIAP may represent a therapeutic strategy for t

265 These observations demonstrate that FLIP is necessary for macrophage differentiation and the

266 Here we report that FLIP has preferential affinity for the alpha1/alpha4 sur

267 Here, we show that FLIP protein expression is downregulated in castrated ra

268 The FLIP algorithm based on the SAF score should decrease in

269 In PTEN-deficient GBM cells, however, the FLIP(S) protein also exhibited a longer half-life than i

270 A FOXO3a binding site was identified in the FLIP promoter and shown necessary for the combined effec

271 ype USP8 decreased the ubiquitination of the FLIP(S) E3 ubiquitin ligase AIP4, an event previously sh

272 Equally surprising was the finding that the FLIP regions necessary for TBK1 inhibition were distinct

273 st reclassified the same slides by using the FLIP algorithm and SAF score, blinded to their first eva

274 dividuals (controls) were evaluated with the FLIP during endoscopy.

275 s able to associate with FLIP(S) or with the FLIP(S)-containing death inducing signal complex.

276 These relative affinities contribute to FLIP being recruited to the DISC at comparable levels to

277 dependent degradation of FLIP(S), leading to FLIP(S) downregulation.

278 Transgenic FLIP was expressed on CD4(+) and CD8(+) T cells and B ce

279 e results suggest that effects of transgenic FLIP on a particular autoimmune disease vary, depending

280 53), induced apoptosis in Nutlin-3A-treated, FLIP(L)-depleted cells, albeit to a lesser extent than i

281 s a key regulator of FLIP(S) ubiquitination, FLIP(S) stability, and TRAIL sensitivity and also define

282 be detected in patients with achalasia using FLIP topography.

283 distention in patients with achalasia using FLIP topography.

284 expresses readily detectable monocistronic v-FLIP mRNAs that are undetectable in wild-type (WT) infec

285 The overexpression of v-FLIP by codon-optimized latent genomes results in a 5- t

286 ically increases the steady-state level of v-FLIP mRNA, at least in part by increasing mRNA stability

287 When codon-optimized v-FLIP sequences are reintroduced into intact KSHV genomes

288 c synergy between the latent KSHV proteins v-FLIP and v-cyclin during KSHV persistent infection that

289 cellular FLICE-inhibitory proteins (termed v-FLIP) that activates NF-kappaB and can trigger important

290 Here we show that codon usage in the v-FLIP gene is strikingly suboptimal.

291 The MC159 protein is a viral FLIP and, as such, possesses two tandem death effector d

292 The KSHV latency-associated viral FLIP (vFLIP) gene induced the expression of IL-1beta, IL

293 son of mechanistic differences between viral FLIP proteins can provide new means of precisely manipul

294 l-2 (vBcl-2) in vesicle nucleation, by viral FLIP (vFLIP) in vesicle elongation, and by K7 in vesicle

295 risingly, transgenic expression of the viral FLIP MC159 from molluscum contagiosum virus (MCV) in mic

296 Viral FLIPs (Fas-linked ICE-like protease [FLICE; caspase-8]-l

297 d state that was less able to associate with FLIP(S) or with the FLIP(S)-containing death inducing si

298 8 protein level is inversely correlated with FLIP level in vivo.

299 and patterns of contractility detected with FLIP topography may represent variations in pathophysiol

300 strated that Akt-1 physically interacts with FLIP(L).