ライフサイエンスコーパス: EWS

1 EWS (Ewing sarcoma) encodes an RNA/ssDNA binding protein

2 EWS inactivation leads to increased ubiquitination and p

3 EWS significantly increased in the 3 days preceding grad

4 EWS-ATF1 activates the melanocyte transcription factor M

5 EWS-ATF1, the fusion product of a balanced chromosomal t

6 EWS-ETS fusions efficiently induced Ewing's sarcoma-like

7 EWS-FLI1 also alters splicing by directly binding to kno

8 EWS-FLI1 alters gene expression through mechanisms that

9 EWS-FLI1 harbors a strong transactivation domain from EW

10 EWS-FLI1 is a disordered protein that precludes standard

11 EWS-FLI1 is an Ewing sarcoma (ES) oncoprotein with an in

12 EWS-FLI1 is an oncogenic fusion protein implicated in th

13 EWS-FLI1 modulation of mRNA splicing may provide insight

14 EWS-Fli1 translocations were analyzed by RNA sequencing

15 EWS-WT1 expression led to a dramatic induction of many n

16 EWS-WT1 functions as an aberrant transcription factor th

17 EWS/FLI binds GGAA-microsatellite sequences in vivo and

18 EWS/FLI functions as a transcriptional activator and tra

19 EWS/FLI functions as an aberrant ETS-type transcription

20 EWS/FLI functions as an aberrant transcription factor to

21 EWS/FLI regulates myriad genes required for Ewing sarcom

22 EWS/FLI-1 siRNA reduces BRN3A expression and promoter ac

23 EWS/FLI1 directly bound and activated the CASP3 promoter

24 EWS/FLI1 encodes an aberrant transcription factor with o

25 EWS/FLI1 is a fusion gene product generated by a chromos

26 EWS/FLI1-activated transcript 2 (EAT-2)A and EAT-2B are

27 ormerly observed in patients with non-type 1 EWS-FLI1 fusions.

28 The type 1 EWS-FLI1 transcript is created as a result of fusion bet

29 The hallmark of this disease is a EWS-WT1 translocation resulting from apposition of the E

30 in the ETS domain of the FLI1 part abolished EWS-FLI1 ubiquitination and stabilized the protein postt

31 esized that coexpression of the SLAM adapter EWS-FLI1-activated transcript 2 (EAT-2) along with a pat

32 em-loop region, contributed to high affinity EWS binding and sequence swap experiments between target

33 n, or the combination were evaluated against EWS, osteosarcoma, and rhabdomyosarcoma xenografts.

34 its relevance to cancer and possibly aging, EWS is likely to play a significant role in maintaining

35 Here we show that miR-22, an EWS/Fli1-repressed miR, is inhibitory to Ewing Sarcoma c

36 lished promoter of cancer metastasis, and an EWS/ETS-repressed target gene.

37 hibition of the analogues was measured by an EWS-FLI1/NR0B1 reporter luciferase assay and a paired ce

38 mplete responses of all treated tumors in an EWS-FLI1-driven mouse xenograft model of ESFT.

39 arkers may be restricted or controlled in an EWS/ETS-dependent manner.

40 We now demonstrate the critical role of an EWS/FLI-bound GGAA-microsatellite in regulation of the N

41 s BRN3A expression and promoter activity and EWS/ETS proteins are bound to the BRN3A locus, suggestin

42 FT originates in mesenchymal stem cells, and EWS/ETS fusion proteins characteristic of EFT activate n

43 ively impaired and altered in EFT cells, and EWS/FLI-1 siRNA can restore some BRN3A function.

44 at the genome-wide localization of NR0B1 and EWS/FLI overlapped as well, suggesting that they regulat

45 Further analysis revealed that NR0B1 and EWS/FLI physically interact.

46 The relationship between tumor response and EWS gene translocation status and IGF-1 levels was evalu

47 to recapitulate BAF complex retargeting and EWS-FLI1 activities.

48 ns in one model each of rhabdomyosarcoma and EWS, and in three of four osteosarcoma models.

49 lonRgamma, spleen tyrosine kinase (SYK), and EWS/FLI1-Activated Transcript 2 (EAT-2) in a variegated

50 the loss of ewsa promotes tumorigenesis, and EWS deficiency may contribute to the pathogenesis of EWS

51 R1A-regulated gene set with that of ZEB2 and EWS, which regulates metastasis and neuronal differentia

52 constructs, suggesting that they function as EWS/FLI-response elements.

53 tical requirement of GGAA-microsatellites as EWS/FLI activating response elements in vivo and reveal

54 e formation of a synergistic complex between EWS-FLI1 and E2F3 as the by far most likely mechanism ex

55 l translocations that encode fusions between EWS and ETS family members.

56 sarcoma: to disrupt the interaction between EWS-FLI1 and PARP, and for chemo-potentiation or radio-p

57 ions of actinomycin D preferentially blocked EWS-FLI1 binding to chromatin, and disrupted EWS-FLI1-me

58 rther promotes transcriptional activation by EWS-FLI1.

59 Ewing Sarcoma pathogenesis is driven by EWS/Ets fusion oncoproteins, of which EWS/Fli1 is the mo

60 an aggressive pediatric malignancy driven by EWS/Ets fusion oncoproteins, which are gain-of-function

61 Driven by EWS/Ets, or rarely variant, oncogenic fusions, Ewing Sar

62 nduction and physical recruitment of E2F3 by EWS-FLI1 replacing E2F4 on their target promoters.

63 ogenic transcriptional hierarchy mediated by EWS/FLI than previously suspected, and implicate a new p

64 ogenic transcriptional hierarchy mediated by EWS/FLI than previously suspected, and implicate a new p

65 plicing as an oncogenic process modulated by EWS-FLI1.

66 sly shown that microRNAs (miRs) regulated by EWS/Fli1 contribute to the pro-oncogenic program in Ewin

67 NRNPK-repressed genes and those repressed by EWS-FLI1 and EWSAT1, suggesting that HNRNPK participates

68 l fraction of targets that were repressed by EWS-FLI1 were also repressed by EWSAT1.

69 221/222, 27a and 29a) strongly repressed by EWS/Fli1.

70 d TERT, validate as alternatively spliced by EWS-FLI1.

71 Regions targeted by EWS-FLI are normally repressed and nucleosomal in primar

72 ted transcript 1 [EWSAT1]) is upregulated by EWS-FLI1 in pMPCs.

73 aster regulator of ES, and is upregulated by EWS/FLI via a GGAA microsatellite enhancer element.

74 We found that in tumor cells, EWS-FLI targets regions of the genome distinct from FLI1

75 ncies which frequently harbor characteristic EWS-FLI1 or EWS-ERG genomic fusions.

76 ecular mechanisms through which the chimeric EWS/FLI1 oncoprotein regulates target genes in Ewing sar

77 We next demonstrated that through chimerism, EWS-FLI acquired the ability to alter chromatin.

78 own to inhibit EWS-FLI1 in vitro, a clinical EWS-FLI1-directed therapy has not been achieved.

79 bryonic fibroblasts derived from conditional EWS/FLI1 knock-in embryos, expression of EWS/FLI1 result

80 growth inhibition for human cells containing EWS-FLI1 (TC32 and TC71) and control PANC1 cell lines de

81 Conversely, EWS-FLI1 inactivates conserved enhancers containing cano

82 Conversely, EWS-WT1 silencing in DSRCT cells reduced ASCL1 expressio

83 Whether other critical EWS/FLI targets are also regulated by GGAA-microsatellit

84 We derive EWS statistics from a prehistoric population proxy based

85 omycin D was found to preferentially disrupt EWS-FLI1 binding by comparison to p53 binding to their r

86 EWS-FLI1 binding to chromatin, and disrupted EWS-FLI1-mediated gene expression.

87 e that actinomycin D preferentially disrupts EWS-FLI1 binding to DNA at selected concentrations.

88 erformed morphoproteomic profiling of DSRCT (EWS-WT1), Ewing's sarcoma (EWS-FLI1) and Wilms' tumor (W

89 s two subgroups of target genes to be either EWS-FLI1 protein-dependent or turnover-dependent.

90 hlh-positive fraction alone further enhanced EWS-ETS-dependent tumor induction.

91 rotein EWS and the transcription factor ETS (EWS-ETS) into a fraction of cells enriched for osteochon

92 family of tumors expresses aberrant EWSR1- (EWS) fusion genes that are derived from chromosomal tran

93 The allergic C57BL/6 mice exhibited EWS aversion that was associated with less visceral fat

94 sion patterns to cell line models expressing EWS-FLI1, supporting the clinical relevance of our findi

95 enchymal progenitor cells (pMPCs) expressing EWS-FLI1 in order to identify gene targets of this oncop

96 The aberrant transcription factor EWS-FLI1 drives Ewing sarcoma, but its molecular functio

97 The oncogenic transcription factor EWS-FLI1 requires RHA to enable Ewing sarcoma (ES) oncog

98 antagonist of oncogenic transcription factor EWS-FLI1.

99 oduction of a chimeric transcription factor, EWS-ATF1, which is formed as the result of a disease-spe

100 ression of an aberrant transcription factor, EWS/FLI, the disease is typically aggressive and microme

101 g protein EWS and transcription factor FLI1 (EWS-FLI1) is pathognomonic for Ewing sarcoma.

102 RN3A locus, suggesting a direct function for EWS/ETS proteins in control of BRN3A expression.

103 a previously unknown molecular function for EWS/FLI, demonstrate a more highly coordinated oncogenic

104 a previously unknown molecular function for EWS/FLI, demonstrate a more highly coordinated oncogenic

105 expression of PARP1, which was required for EWS-FLI-mediated transcription, thereby enforcing oncoge

106 We find statistical support for EWSs in advance of population collapse.

107 n through reexpression experiments that full EWS/FLI1-mediated transcriptional repression requires in

108 In contrast, a fully functional EWS/FLI mutant (Mut9, which retains approximately half o

109 The most common fusion, EWS/FLI, consists of an EWSR1-derived strong transcripti

110 rrant transcription factor expression, e.g., EWS-FLI1, c-Myc, n-Myc, and PML-RARalpha.

111 The oncogenic fusion gene EWS-WT1 is the defining chromosomal translocation in des

112 Our findings demonstrate how EWS-FLI1 establishes an oncogenic regulatory program gov

113 In primary endothelial cells, however, EWS-FLI and FLI1 demonstrate similar targeting.

114 usions, and global miR profiling to identify EWS/Fli1-regulated miRs with oncogenesis-modifying roles

115 horylated (p)-mTOR, p-p70S6K; (b) mTORC 2 in EWS and DSRCT; (c) ERK signaling was seen in the advance

116 ine a wider role for GGAA-microsatellites in EWS/FLI function than previously appreciated.

117 ed that trabectedin functionally inactivated EWS-FLI1 by redistributing the protein within the nucleu

118 mber of compounds have been shown to inhibit EWS-FLI1 in vitro, a clinical EWS-FLI1-directed therapy

119 Further, a correlation of growth inhibition (EWS-FLI1 expressing TC32 cells) and the luciferase repor

120 d transcriptional repression requires intact EWS and ETS domains.

121 Our study provides novel insights into EWS-FLI1 turnover, a critical pathway in Ewing sarcoma p

122 One such chimera is EWS-FLI, the most frequently occurring translocation in

123 (of 18-26 GGAA repeats) that confers maximal EWS/FLI-responsiveness to target genes, but the mechanis

124 The mean maximum EWS was significantly higher preceding grade IV/V compli

125 the SLAM signaling pathway adapter molecule EWS-activated transcript 2 (EAT-2) is polymorphic, which

126 EWS-FLI1 with either siRNA or small-molecule EWS-FLI1 inhibitors suppressed the expression of ENT1, E

127 Notably, EWS-FLI1 fusion genes acted in a positive feedback loop

128 ocesses are unlikely to explain the observed EWS patterns.

129 ernative explanatory models for the observed EWS-FLI1/E2F3 cooperation based on longitudinal E2F targ

130 ted as a result of fusion between exons 7 of EWS and 6 of FLI1, and retrospective studies have report

131 A sequencing revealed a marked antagonism of EWS/ETS transcriptional activity in Wnt/beta-catenin-act

132 en for compounds that disrupt the binding of EWS-FLI1 to its cognate DNA targets.

133 ion of (18)F-FLT as a companion biomarker of EWS-FLI1 activity and a novel diagnostic imaging approac

134 Through comparison of EWS/FLI transcriptional profiling and genome-wide locali

135 calization data, we define the complement of EWS/FLI direct downregulated target genes.

136 Complementation of EWS in Ews-deficient cells restores PGC-1alpha and mitoc

137 cussing the implications of the detection of EWS in human systems for archaeology and sustainability

138 defeat a transforming pathway downstream of EWS-ATF1.

139 We evaluate the effect of EWS-FLI1 on posttranscriptional gene regulation using bo

140 Our current study investigates the effect of EWS-FLI1 upon RHA helicase activity.

141 Expression of EWS-FLI results in nucleosome depletion at targeted site

142 Expression of EWS-FLI1 and EWSAT1 repressed gene expression, and a sub

143 requirement for the persistent expression of EWS-FLI1 for cell survival and growth, which is a hallma

144 The inducible expression of EWS-FLI1 in embryoid bodies, or collections of different

145 Expression of EWS-FLI1 in non-ESFT cells increased GLI1 expression and

146 led that DNA damage induced by expression of EWS-FLI1 or EWS-ERG fusion genes was potentiated by PARP

147 cially dependent on continuous expression of EWS-FLI1, its regulation of turnover has not been charac

148 train that permits physiologic expression of EWS-WT1 under the native murine Ews promoter.

149 Paradoxically, expression of EWS/FLI1 in nontransformed primary cells results in apop

150 Importantly, expression of EWS/FLI1 in the mouse triggered an early onset of apopto

151 Ectopic expression of EWS/FLI1 resulted in an increased expression of CASP3 pr

152 nal EWS/FLI1 knock-in embryos, expression of EWS/FLI1 resulted in apoptosis with concomitant increase

153 new foundation to understand the function of EWS in development and disease.

154 The function of EWS-FLI1 is essential for the maintenance of ESFT cell s

155 h are critical for the oncogenic function of EWS-FLI1.

156 R1A is one of the top ranked target genes of EWS/FLI, the master regulator of ES, and is upregulated

157 arget gene repertoire, the identification of EWS-FLI1 target genes that may also point to therapeutic

158 laques as unaffected by chronic ingestion of EWS.

159 ing was the most favorable for inhibition of EWS-FLI1 by analogs of 2.

160 mediated, at least in part, by inhibition of EWS/ETS fusion protein function that results in derepres

161 thus engleri as the most potent inhibitor of EWS-FLI1 induced luciferase reporter expression.

162 e small molecule YK-4-279 is an inhibitor of EWS-FLI1 oncogenic function that disrupts specific prote

163 Knockdown of EWS reduced, whereas overexpression enhanced, the expres

164 small interfering RNA-mediated knockdown of EWS/FLI1 led to a marked decrease in CASP3 transcripts i

165 ity approach, we determined the half-life of EWS-FLI1 to lie between 2 and 4 h, whereas full-length E

166 Loss of EWS leads to a significant decrease in mitochondria abun

167 cells, and the contribution that the loss of EWS makes towards disease pathogenesis is unknown.

168 ble, non-invasive, pharmacodynamic marker of EWS-FLI1 activity.

169 YK-4-279 validates the splicing mechanism of EWS-FLI1, showing alternatively spliced gene patterns th

170 ciency may contribute to the pathogenesis of EWS-fusion-expressing sarcomas.

171 lls through a decrease in phosphorylation of EWS-FLI1 and its ability to bind DNA.

172 arcomas are characterized by the presence of EWS/ETS fusion genes in the absence of other recurrent g

173 This process is a neomorphic property of EWS-FLI1 compared to wild-type FLI1 and depends on tyros

174 We report a novel RNA binding property of EWS-FLI1 leading us to discover that YK-4-279 inhibition

175 3) caused the same nuclear redistribution of EWS-FLI1, leading to a loss of activity at the promoter,

176 Reduction of EWS-FLI1 produces an isoform of gamma-TERT that has incr

177 notecan treatment was a complete reversal of EWS-FLI1 activity and elimination of established tumors

178 These results demonstrate a novel role of EWS in mitochondrial and cellular energy homeostasis by

179 In this study, we uncovered a new role of EWS in mitochondrial homeostasis and energy metabolism.

180 similar expression profile, the main role of EWS-FLI1 could be through maintenance of stemness and ne

181 owever, despite the well-established role of EWS-FLI1 in tumor initiation, the development of models

182 and show the cell context-dependent roles of EWS/FLI1 in apoptosis and tumorigenesis.

183 tion at targeted sites, whereas silencing of EWS-FLI in tumor cells restored nucleosome occupancy.

184 In this report, we show that silencing of EWS-FLI1 with either siRNA or small-molecule EWS-FLI1 in

185 Silencing of EWS/FLI in patient-derived tumor cells results in the al

186 We employed stable silencing of EWS/Fli1, the most common of the oncogenic fusions, and

187 Knockdown mediated by siRNA of EWS-FLI1 abrogated this sensitivity to olaparib (Figure

188 h GLI1 as a direct transcriptional target of EWS-FLI1 and suggest a potential role for GLI1 in ESFT t

189 reveal that EWSAT1 is a downstream target of EWS-FLI1 that facilitates the development of Ewing sarco

190 d GLI1 as a direct transcriptional target of EWS-FLI1.

191 de insight into the therapeutic targeting of EWS-FLI1.

192 regulatory proteins are dominant targets of EWS/FLI-mediated transcriptional repression.

193 f a migratory phenotype, and upregulation of EWS/ETS-repressed genes.

194 ies, using recombinant Delta22 (a version of EWS/FLI containing only the FLI portion), demonstrate a

195 of anti-Ova IgE antibodies after 5 weeks of EWS intake compared to controls.

196 ignaling is abrogated by the driver oncogene EWS-FLI1.

197 coma tumors is driven by the fusion oncogene EWS-FLI1.

198 nslocated prion-like domain of the oncogenic EWS-FLI1 fusion protein enables phase-separation events,

199 Tumor cells express the chimeric oncoprotein EWS-FLI1 from a specific t(22;11)(q24;12) translocation.

200 reliance on the ETS-type fusion oncoprotein EWS/FLI.

201 damage induced by expression of EWS-FLI1 or EWS-ERG fusion genes was potentiated by PARP1 inhibition

202 frequently harbor characteristic EWS-FLI1 or EWS-ERG genomic fusions.

203 p between tumor response and IGF-1 levels or EWS gene translocations was observed.

204 iniscent of Ewing sarcoma cells with partial EWS/ETS loss of function.

205 Physiologically, EWS has diverse and essential roles in various organ dev

206 tudy, we investigated the specific processes EWS/FLI1 utilizes to alter gene expression.

207 ranslocation between the RNA binding protein EWS and one of five ETS transcription factors, most comm

208 f the genes encoding the RNA-binding protein EWS and the transcription factor ETS (EWS-ETS) into a fr

209 on of the genes encoding RNA-binding protein EWS and transcription factor FLI1 (EWS-FLI1) is pathogno

210 ic potential is driven by a chimeric protein EWS-ATF1 (Ewing's sarcoma protein-activating transcripti

211 sarcomas (ESs), the oncogenic fusion protein EWS-FLI1 prevents mesenchymal differentiation and induce

212 o expression of the oncogenic fusion protein EWS-FLI1.

213 The Ewing Sarcoma protein (EWS) is a multifaceted RNA binding protein (RBP) with es

214 These sequences provide EWS/FLI-mediated activation to reporter constructs, sugg

215 By generating high quality EWS-RNA interactome, we uncovered its specific and preva

216 icing toward oncogenesis, and, reciprocally, EWS-FLI1 interactions with splicing proteins may inform

217 ermined the binding affinity for recombinant EWS-FLI1 (Kd = 4.8 +/- 2.6 muM).

218 idine positron emission tomography) reflects EWS-FLI1 activity in Ewing sarcoma cells both in vitro a

219 tive complications can be preceded by rising EWS.

220 In Ewing sarcoma (EWS) cell lines, CP751,871 inhibited growth poorly (<50%

221 at a multifunctional protein, Ewing Sarcoma (EWS), is essential for determining brown fat lineage dur

222 the fused in sarcoma (FUS), Ewings sarcoma (EWS), and TAF15 genes are translocated onto a variety of

223 ting from apposition of the Ewing's sarcoma (EWS) gene with the Wilms' tumor (WT1) gene.

224 ofiling of DSRCT (EWS-WT1), Ewing's sarcoma (EWS-FLI1) and Wilms' tumor (WT1) to better understand th

225 The oncoprotein in Ewing sarcoma, EWS-FLI1, is proposed to interact with PARP-1, driving P

226 We examined whether an early warning score (EWS) could predict inpatient complications in surgical p

227 stical tests known as early warning signals (EWSs).

228 cells (MPCs) transformed with the signature EWS-FLI1 translocation, the hallmark of Ewing's sarcoma

229 s, both of which were abrogated by silencing EWS-WT1.

230 ion factors, their formation leaves a single EWS allele in the sarcoma cells, and the contribution th

231 rgy was induced using an egg white solution (EWS) in ovalbumin- (OVA-) sensitized C57BL/6 and low-den

232 of the European Union Early warning system (EWS), 73 NPS were officially identified for the first ti

233 novel MTM analogues that selectively target EWS-FLI1 or other oncogenic transcription factors, as an

234 rated by quantitative pre-mRNA analysis that EWS/FLI1 repressed the expression of previously validate

235 We conclude that EWS-FLI1 modulates RHA helicase activity causing changes

236 These results demonstrate that EWS is essential for early brown fat lineage determinati

237 We demonstrate that EWS, along with its binding partner Y-box binding protei

238 Together these data demonstrate that EWS/FLI1 can dictate steady-state target gene expression

239 Mechanistic analyses demonstrated that EWS-WT1 directly bound the proximal promoter of ASCL1, a

240 We find that EWS-FLI1 reprograms gene regulatory circuits in Ewing sa

241 In a CLIP-seq experiment, we find that EWS-FLI1 RNA-binding motifs most frequently occur adjace

242 pression, as reported earlier, we found that EWS was able to enhance the recruitment of Drosha to chr

243 We found that EWS-FLI1 reduces RHA helicase activity in a dose-depende

244 We found that EWS/FLI directly binds the GSTM4 promoter, and regulates

245 Confirming this, we found that EWS/FLI1 decreased the transcript half-life of insulin-l

246 These results extend the hypothesis that EWS/ETS proteins induce expression of neuronal markers s

247 Taken together, our findings reveal that EWS-WT1 can activate neural gene expression and direct p

248 an orthotopic xenograft model, we show that EWS/FLI-induced repression of alpha5 integrin and zyxin

249 ChIP experiments showed that EWS/FLI1 decreases the amount of Pol II at the promoter

250 Together, these findings suggest that EWS may positively and negatively regulate miRNA biogene

251 Taken together, these data suggest that EWS/FLI and NR0B1 physically interact, coordinately modu

252 These two features suggest that EWS/FLI is the primary mutation that drives the developm

253 These findings suggest that EWS/FLI1 induces apoptosis, at least partially, through

254 Recent evidence suggests that EWS-FLI1 increases expression of GLI1 by an unknown mech

255 The EWS calculated using vital signs has been developed to i

256 The EWS-ETS family of gene fusions and their downstream effe

257 ng a chromosomal translocation affecting the EWS locus.

258 tification of its key driver alteration, the EWS-FLI1 gene fusion that encodes this aberrant, chimeri

259 ind that the BAF complex is recruited by the EWS-FLI1 fusion protein to tumor-specific enhancers and

260 ressive pediatric malignancies driven by the EWS-FLI1 fusion protein, an aberrant transcription facto

261 ptional derepression of IGF signaling by the EWS/Fli1 fusion oncoprotein via miRs.

262 signs and neurologic status to calculate the EWS for each postoperative vital set measured on the war

263 ) chromosomal translocation that encodes the EWS/FLI oncoprotein.

264 Most cases of Ewing's sarcoma express the EWS/FLI fusion protein.

265 Ewing sarcoma usually expresses the EWS/FLI fusion transcription factor oncoprotein.

266 n vivo and reveal an unexpected role for the EWS portion of the EWS/FLI fusion in binding to sweet-sp

267 d energy metabolism in cancers harboring the EWS translocation.

268 vity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to pol

269 Here, we identify the EWS-FLI1 protein as a substrate of the ubiquitin-proteas

270 Fusion of the EWS gene to FLI1 produces a fusion oncoprotein that driv

271 ut9, which retains approximately half of the EWS portion of the fusion) showed low affinity for small

272 Conditional expression of the EWS-ATF1 human cDNA in the mouse generates CCS-like tumo

273 Genes downstream of the EWS-ETS fusion protein were quite transcriptionally acti

274 The many insights into the biology of the EWS-FLI1 protein in the initiation and progression of ES

275 yses, to provide a comprehensive view of the EWS-FLI1 target gene repertoire, the identification of E

276 ue tumor that depends on the activity of the EWS-FLI1 transcription factor for cell survival.

277 it depends on the continued activity of the EWS-FLI1 transcription factor to maintain the malignant

278 n unexpected role for the EWS portion of the EWS/FLI fusion in binding to sweet-spot GGAA-microsatell

279 d transcriptional repressive function of the EWS/FLI fusion is also required for the transformed phen

280 enantiomers, only (S)-YK-4-279 reverses the EWS-FLI1 inhibition of RHA helicase activity.

281 a strong preclinical rationale to target the EWS-FLI1:PARP1 intersection as a therapeutic strategy to

282 Thus, the EWS-FLI chimera acquired chromatin-altering activity, le

283 rity comparable to what is observed when the EWS/FLI oncogene expression is compromised.

284 A threshold EWS of 8 predicted occurrence of grade IV/V complication

285 r that YK-4-279 inhibition of RHA binding to EWS-FLI1 altered the RNA binding profile of both protein

286 pound from the screen, blocks RHA binding to EWS-FLI1, induces apoptosis in ESFT cells and reduces th

287 nd regulatory potential in other cell types, EWS-FLI1 multimers induce chromatin opening and create d

288 nstrate that LOX is a previously undescribed EWS/FLI-repressed target that inhibits the transformed p

289 ive E2F4/p130 complexes on target genes upon EWS-FLI1 modulation.

290 Using EWS-FLI and its parental transcription factor, FLI1, we

291 k for analyzing societal regime shifts using EWS at large spatial and temporal scales.

292 -nine percent of identified transcripts were EWS-FLI1, and of these, 58.8% were type 1.

293 ional studies are needed to evaluate whether EWS can reduce the severity of postoperative complicatio

294 This study explores whether EWSs anticipated human population collapse during the Eu

295 ven by EWS/Ets fusion oncoproteins, of which EWS/Fli1 is the most common.

296 the NuRD co-repressor complex interacts with EWS/FLI, and that its associated histone deacetylase and

297 needed to understand how MTM interferes with EWS-FLI1.

298 e small molecule trabectedin interferes with EWS-FLI1.

299 ene patterns that significantly overlap with EWS-FLI1 reduction and WT human mesenchymal stem cells (

300 Relationship with EWS and timing of complication was assessed using Kruska