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 have a promising potential to not only be used to mo

3 EWS inactivation leads to increased ubiquitination and p

4 EWS significantly increased in the 3 days preceding grad

5 EWS-ATF1 activates the melanocyte transcription factor M

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

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

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

9 EWS-FLI1 alters gene expression through mechanisms that

10 EWS-FLI1 harbors a strong transactivation domain from EW

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 protein interacts with the RNA helicase DHX9 an

15 EWS-Fli1 translocations were analyzed by RNA sequencing

16 EWS-FLI1, the oncogenic driver of Ewing sarcoma, regulat

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

18 EWS-WT1 functions as an aberrant transcription factor th

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

20 EWS/FLI functions as a transcriptional activator and tra

21 EWS/FLI regulates myriad genes required for Ewing sarcom

22 EWS/FLI1 directly bound and activated the CASP3 promoter

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

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

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

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

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

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

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

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

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

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

33 for screening for modulators of FUS-CHOP and EWS-FLI phase separation.

34 development of yeast models of FUS-CHOP and EWS-FLI toxicity and aggregation.

35 oma patient cells harboring the FUS-CHOP and EWS-FLI translocations.

36 The resulting fusion proteins, FUS-CHOP and EWS-FLI, drive aberrant transcriptional programs that un

37 the toxicity and aggregation of FUS-CHOP and EWS-FLI.

38 ing as a downstream target of both MEIS1 and EWS-FLI1, is also characterized as a novel tumor-promoti

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

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

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

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

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

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

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

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

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

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

49 rther promotes transcriptional activation by EWS-FLI1.

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

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

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

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

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

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

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

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

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

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

60 221/222, 27a and 29a) strongly repressed by EWS/Fli1.

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

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

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

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

65 index of dispersion, are promising candidate EWS for detecting disease emergence.

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

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

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

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

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

71 ed by a chimeric oncoprotein, most commonly, EWS-FLI1.

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

73 Conversely, EWS-FLI1 inactivates conserved enhancers containing cano

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

75 We derive EWS statistics from a prehistoric population proxy based

76 Pharmacologic impairment of DHX9/EWS-FLI1 interaction promoted RNA-dependent association

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

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

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

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

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

82 rnative complexes formed by DHX9 with either EWS-FLI1 or pncCCND1_B-Sam68.

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

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

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

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

87 Additionally, we explore EWS calculated on the rate of incidence over time, a pro

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

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

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

91 inhibits the oncogenic transcription factor EWS-FLI1 in Ewing sarcoma, but poor pharmacokinetics (PK

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

93 antagonist of oncogenic transcription factor EWS-FLI1.

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

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

96 For EWS to be useful at detecting future (re-)emergence, CSD

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

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

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

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

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

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

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

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

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

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

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

108 In this work we identify EWS for incidence data, the standard data type collected

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

110 ed transcripts are significantly enriched in EWS-FLI1 target genes, contribute to the aberrant transc

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

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

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

114 d transcriptional repression requires intact EWS and ETS domains.

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

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

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

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

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

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

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

122 ocesses are unlikely to explain the observed EWS patterns.

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

124 gues inhibit the transcriptional activity of EWS-FLI1.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

146 laques as unaffected by chronic ingestion of EWS.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

191 The best performing EWS were the mean and variance, with AUC > 0.75 one year

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

193 Previously, potential EWS have been identified for prevalence data, however th

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

195 S growth, and ARID1A-L reciprocally promotes EWS-FLI1 protein stability.

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

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

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

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

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

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

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

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

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

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

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

207 tive complications can be preceded by rising EWS.

208 We identify Ewing sarcoma (EWS) protein as a novel LTbetaR signaling component that

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

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

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

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

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

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

215 nd functional studies included WT1 ChIP-seq, EWS-WT1 knockdown using JN-DSRCT-1 cells and immunohisto

216 We also evaluated the performance of seven EWS: the autocorrelation, coefficient of variation, inde

217 Early warning signals (EWS) identify systems approaching a critical transition,

218 gence using CSD-based early-warning signals (EWS), which are statistical moments estimated from time

219 e-)emergence based on early warning signals (EWSs) derived from the theory of critical slowing down.

220 Early warning signals (EWSs) offer the hope that patterns observed in data can

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

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

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

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

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

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

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

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

229 We conclude that EWS limits expression of proinflammatory molecules, GM-C

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

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

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

233 Epigenomic analyses demonstrate that EWS-FLI1, the primary fusion driver for this cancer, dir

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

235 Recent work demonstrated that EWS-FLI1, the oncogenic driver of Ewing sarcoma (ES), pl

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

237 We show, through several examples, that EWS calculated on simulated incidence time series data e

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

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

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

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

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

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

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

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

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

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

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

249 The EWS:TRAF3 complex forms under unligated conditions that

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

251 e identified a direct connection between the EWS-FLI1 protein and ARID1A isoform protein variant ARID

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

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

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

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

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

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

258 osomal translocation t(11;22) generating the EWS-FLI1 oncogene.

259 d energy metabolism in cancers harboring the EWS translocation.

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

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

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

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

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

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

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

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

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

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

270 oints whose expression is independent of the EWS-WT1 fusion gene in cultured DSCRT cells.

271 ere both highly expressed and targets of the EWS-WT1 fusion protein.

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

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

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

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

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

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

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

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

280 LDHA is a pharmacologically tractable EWS-FLI1 transcriptional target that regulates the glyco

281 In addition to regulating transcription, EWS-FLI1 also alters the splicing of many mRNA isoforms,

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

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

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

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

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

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

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

289 We assess whether EWSs are present prior to the recovery of overexploited

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

291 r report a novel feed-forward cycle in which EWS-FLI1 leads to preferential splicing of ARID1A-L, pro

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

293 regulating the epigenome in cooperation with EWS-FLI1, occupying 77.2% of promoters and 55.6% of enha

294 the specific BAF subunits that interact with EWS-FLI1 and the precise role of the BAF complex in ES o

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

296 e small molecule trabectedin interferes with EWS-FLI1.

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

298 ncer-driven oncogene, which co-operates with EWS-FLI1 in transcriptional regulation, and plays a key

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