ライフサイエンスコーパス: GLI1

1 sed K48-linked ubiquitination/degradation of GLI1.

2 isms, all triggering the downstream effector Gli1.

3 moothened (Smo) and the transcription factor Gli1.

4 by genetic or pharmacological inhibition of Gli1.

5 c strategy in treating tumors that expresses Gli1.

6 t AKT1 is a direct transcriptional target of GLI1.

7 letions that fuse the promoter of INHBE with GLI1.

8 , SOX9, AMH, CYP17A1, LIN28, WNT2B, ETV5 and GLI1.

9 erived Hedgehog signals, become positive for GLI1.

10 inhibits ciliary PKA activity, and increases Gli1.

11 Treatment with GANT61, a GLI1/2 inhibitor, but not with IPI 926, a Smoothened inh

12 re not able to give rise to eRMS upon Smo or Gli1/2 overactivation in vivo, suggesting that Hh-induce

13 We also identified that GLI1, a candidate stem cell-associated gene, is signific

14 roteins bind to and suppress the promoter of GLI1, a critical mediator of progesterone action in the

15 dent editing and transcriptional activity of GLI1, a Hedgehog (Hh) pathway transcriptional activator

16 scendants within the adrenal capsule express Gli1, a known marker of progenitors of steroidogenic adr

17 Here, we extend these findings to identify GLI1, a transcriptional effector of the Hedgehog pathway

18 tem cells, identified by their expression of Gli1, a transcriptional effector of the sonic hedgehog p

19 pathway blockade with cyclopamine suppressed GLI1 activation and enhanced tumor sensitivity to radiot

20 le binding to Gli1 zinc finger and impairing Gli1 activity by interfering with its interaction with D

21 TGFbeta stimulates GLI1 activity in cancer cells and requires its transcrip

22 nsequence of its robust inhibitory effect on Gli1 activity, Glabrescione B inhibited the growth of He

23 cal Hedgehog signaling, a known regulator of Gli1 activity, is required for pancreas recovery.

24 Strikingly, this partial loss of Gli1 affects activated fibroblasts in the pancreas and t

25 GLI1 alone is sufficient to drive UGT1A-dependent glucur

26 ibroblast-specific deletion of Gli2, but not Gli1, also limited kidney fibrosis, and induction of myo

27 Indeed, surviving N/TERT-GLI1 and -GLI2 cells expressed higher levels of the epit

28 Compared with control and untreated N/TERT-GLI1 and -GLI2 cells, those that survived genotoxic insu

29 in the downstream transcriptional activator GLI1 and a decrease in the GLI3 transcriptional represso

30 l effect of IKBKE involves the activation of GLI1 and AKT signaling and is independent of the levels

31 Here we show that GLI1 and an active mutant of GLI2 (DeltaNGLI2) promote a

32 ablished a novel connection between aberrant Gli1 and Bid in the survival of tumor cells and their re

33 lies having biallelic truncating variants in GLI1 and developmental defects overlapping with Ellis-va

34 Our study reported aberrant Gli1 and Gli2 activation in a large majority of tissues.

35 gehog (Hh) pathway transcriptional effectors GLI1 and GLI2 are expressed in myofibroblast progenitors

36 rely on direct transcriptional repression of Gli1 and Gli2 effectors of the SHH pathway, through recr

37 Finally, we identified that Gli1 and Gli2 exhibited different functions in the regul

38 In summary, our results show that GLI1 and GLI2 facilitate the propagation of cells with d

39 The transcription factors GLI1 and GLI2 have been implicated in both the initiatio

40 n studies reveal that BRD4 directly occupies GLI1 and GLI2 promoters, with a substantial decrease in

41 Knockdown of GLI1 and GLI2 restored sensitivity to vemurafenib-resist

42 Finally, GLI1 and GLI2 were upregulated in the kidneys of patient

43 trast, GANT61 (a small molecule inhibitor of Gli1 and Gli2) induced autophagy, as determined by immun

44 f the activators of this family of proteins (Gli1 and Gli2) inhibited the proliferation of p63(+) and

45 n and mouse reporter strains for Shh, Ptch1, Gli1 and Gli2-expression and proliferation markers to id

46 g the abundance of the transcription factors GLI1 and GLI3.

47 broblasts, recombinant Shh protein activated Gli1 and induced alpha-smooth muscle actin (alpha-SMA),

48 t that are marked by the expression of Wnt2, Gli1 and Isl1.

49 mechanism that uses the transcription factor GLI1 and its associated complex as a central effector to

50 AA-induced apoptosis and down-regulation of GLI1 and NFATc1 activation, indicating that NFATc1 activ

51 The expression of the direct Hh targets, Gli1 and Patched 1, is inhibited, while the expression o

52 Furthermore, co-inhibition of GLI1 and PI3K induced apoptosis of hematopoietic stem/pr

53 K gene PIK3CA was attenuated by antagonizing GLI1 and PI3K.

54 dgehog signaling, using the pathway readouts Gli1 and Ptch1 as a model system.

55 ular chondrocytes such that the induction of GLI1 and PTCH1 expression is reduced by 71 and 55%, resp

56 uccessfully predicting expression changes of Gli1 and Ptch1 in mutants at different developmental sta

57 A genome-scale analysis of DNA binding by Gli1 and Sox2, a pan-neural determinant, identified a se

58 fied a new transcriptional complex including GLI1 and the TGFbeta-regulated transcription factor, SMA

59 our data suggest a novel drug combination of Gli1 and Top1 inhibitors as an effective therapeutic str

60 Furthermore, co-localization of GLI1(+) and MKX(+) cells is also found in human tendinop

61 cription factor glioma-associated protein 1 (GLI1) and the UDP glucuronosyltransferase (UGT1A) family

62 The expression of Shh, Gli1, and Ngn1 proteins was higher and BMP4 protein was

63 ferative expansion during fibrosis, and both Gli1- and Gli2-positive cells differentiated into alpha-

64 digit 1 field and preaxial polydactyly in a Gli1- and Gli3-dependent manner.

65 Here, we show that Ptc1 and Gli1 are significantly deficits in the hippocampus of an

66 fy the Hedgehog pathway transcription factor GLI1 as a critical driver of lung SCC.

67 more, we identified the transcription factor GLI1 as a novel target of the SULF2-WNT cascade.

68 ate a novel mechanism underlying the role of GLI1 as an effector of TGFbeta signaling in the regulati

69 d expression of the HhP transcription factor GLI1 as they became resistant after long-term EGFR inhib

70 tes with key transcription factors including Gli1, Atoh1 and REST to regulate the expression of both

71 ating tissue regeneration and define the WNT-GLI1 axis as a novel downstream effector for this sulfat

72 showed that SHH signaling activated the SHH/GLI1/BCL-2 axis, leading to the inhibition of myeloma ce

73 We found that both GLI3 and GLI1 bind to the pluripotency factor NANOG.

74 is of the Bid promoter identified a putative Gli1 binding site, and further studies using luciferase

75 nes associated with medulloblastoma-specific GLI1 binding sites are downregulated in response to JQ1

76 Sonic hedgehog induces GLI1 binding to the IL-6 promoter and increases IL-6 exp

77 Falpha) mediated IKKbeta activation-impaired GLI1 binding with the E3 ubiquitin ligase-ITCH, leading

78 GLI1 binds to the cyclin d1 promoter and regulates its a

79 GLI1 binds to the IL-6 mouse promoter and regulates the

80 ation, and expression studies, we found that GLI1 binds to the promoter of these antiapoptotic molecu

81 found for the first time that tGLI1, but not GLI1, binds to and enhances the human vascular endotheli

82 mutations) as a model, we show that loss of GLI1 blocks the progression of KRAS-induced pancreatic p

83 was ineffective, indicating that the role of Gli1 both in augmenting hedgehog signalling and in retar

84 mouse Gli1 gene, repressing the induction of Gli1 by SHH by binding to both GATA and Gli binding site

85 e detected in tumor tissue in the absence of GLI1 by TUNEL staining.

86 RNA oligonucleotide significantly decreased GLI1, c-myc, and CD44 mRNA levels, in a panel of colon a

87 geting of Gli proteins with GANT61 inhibited Gli1(+) cell expansion and myofibroblast differentiation

88 acing studies demonstrated that the original Gli1+ cell population had the capacity to heal immature

89 s, the level of induction was weak in N/TERT-GLI1 cells, indicating that GLI1 may activate anti-apopt

90 Genetic ablation of Gli1(+) cells abolished BMF and rescued bone marrow fail

91 Our data indicate that Gli1(+) cells are a major source of osteoblast-like cell

92 These findings implicate Gli1(+) cells as critical adventitial progenitors in vas

93 Genetic ablation of Gli1(+) cells before induction of kidney injury dramatic

94 Finally, postnatal Gli1(+) cells contribute to both chondrocytes and osteob

95 In vitro, Gli1(+) cells express typical MSC markers, exhibit trili

96 Here, we show that Gli1(+) cells located in the arterial adventitia are pro

97 in fetal or postnatal mice, we discover that Gli1(+) cells progressively produce osteoblasts in all s

98 s that tissue-resident, but not circulating, Gli1(+) cells proliferate after kidney, lung, liver, or

99 Most notably, in postnatal growing mice, the Gli1(+) cells residing immediately beneath the growth pl

100 Likewise, incisor Gli1(+) cells, but not NG2(+) cells, exhibit typical MSC

101 lation supporting mouse molar root growth as Gli1(+) cells.

102 To further examine the involvement of Gli1+ cells and hedgehog signaling in enthesis healing,

103 In contrast, injured mature entheses had few Gli1+ cells early in the healing process, with limited r

104 represent an MSC subpopulation derived from Gli1+ cells; they express classical MSC markers and cont

105 Moreover, we provide evidence that GLI1 contributes to the survival of diffuse large B-cell

106 findings define a novel pathway regulated by GLI1 controlling pancreatic tumor progression and provid

107 Using bigenic Gli1-CreER(t2); R26tdTomato reporter mice, we observed i

108 CreER(T), GFAP-CreER(T2), Sox2(CreERT2), and Gli1(CreERT2) and were long-lived in vivo.

109 Glioma-associated oncogene (Gli1)-CreERT2 and Patched (Ptch)-lacZ reporter mice were

110 IKKbeta-GLI1 crosstalk is significant because combined inhibitio

111 on in part via the activation of a novel WNT-GLI1-CYCLIN D1 pathway.

112 Conversely, complementation of Bid in Gli1-deficient cells restored CPT-induced Chk1 phosphory

113 SLFN4+ MDSCs were not observed in infected GLI1-deficient mice.

114 nts with homozygous C-terminal truncation of GLI1 demonstrated that the corresponding mutant GLI1 pro

115 r, these results indicate that SLFN4 marks a GLI1-dependent population of MDSCs that predict a shift

116 s using luciferase reporter assays confirmed Gli1-dependent promoter activity.

117 Mice lacking GLI1 develop only low-grade lesions at low frequency, an

118 tification of the structural requirements of Gli1/DNA interaction highlights their relevance for phar

119 Using a Gli1-driven Cre-mediated recombination system, our resul

120 Here, we demonstrated that GLI2, but not GLI1, drives myofibroblast cell-cycle progression in cul

121 ith upregulation of the transcription factor GLI1 Ectopic expression of SHH or IHH in mouse T cells i

122 lations of fetal cells (fetal cortex derived Gli1-expressing cells and mesenchymal Tcf21-expressing m

123 fate during regeneration, we uncovered that Gli1-expressing cells exhibit long-term self-renewal cap

124 Notably, we observed that innervated Gli1-expressing progenitors within mechanosensory touch

125 importance of CRD-BP-dependent regulation of GLI1 expression and activities in the development of BCC

126 t-induced and CRD-BP-dependent regulation of GLI1 expression and activities is important for the deve

127 er characterization showed that AA represses GLI1 expression by stimulating nuclear translocation of

128 In breast tumor tissues, GLI1 expression enhanced tissue identification and discr

129 WNT induces GLI1 expression in a SULF2- and beta-CATENIN-dependent m

130 ame pathway is also active in human BMF, and Gli1 expression in BMF significantly correlates with the

131 her Hedgehog pathway agonists did not affect GLI1 expression in lung SCC cells.

132 nerves secrete Shh protein, which activates Gli1 expression in periarterial cells that contribute to

133 Here, we report that increased GLI1 expression in the leading edge of HNSCC tumors is f

134 Finally, restoring GLI1 expression in the liver of SULF2-KO mice after PH r

135 In eutopic endometrium, GLI1 expression is reduced in women with endometriosis.

136 and hedgehog signaling in enthesis healing, Gli1 expression was examined via lineage tracing approac

137 Moreover, Shh and Gli1 expression was increased in Tmem107(-/-) animals as

138 Furthermore, radiotherapy-induced GLI1 expression was mediated in part by the mTOR/S6K1 pa

139 However, GLI1 expression was modulated by either inhibition or ac

140 ure injured entheses retained high levels of Gli1 expression, a marker of hedgehog activation, consis

141 y bind to the GLI1 promoter, thus inhibiting GLI1 expression, and loss of ARP-T1 led to activation of

142 vels, but not those with low or undetectable GLI1 expression, were sensitive to hedgehog pathway inhi

143 erses the ability of GATA factors to repress Gli1 expression.

144 difying SMO-activated GLI2 translocation and GLI1 expression.

145 e paralleled the domain of reduced Foxf2 and Gli1 expression.

146 Using genetic-inducible lineage tracing for Gli1-expression, we found that Shh-responding cells cont

147 he transcriptional activity of the truncated GLI1 factor was found to be severely impaired by cell cu

148 uctural requirements of the pathway effector Gli1 for binding to DNA and identify Glabrescione B as t

149 nstrate that SMAD4 physically interacts with GLI1 for concerted regulation of gene expression and cel

150 tron regions of ROS1 target genes, CXCL1 and GLI1, for upregulating their expressions.

151 u, mediated by Fbxl17, allows the release of Gli1 from Sufu for proper Hh signal transduction.

152 ZFPM1) to the regulatory region of the mouse Gli1 gene, repressing the induction of Gli1 by SHH by bi

153 RNA levels of the GLI family zinc finger 1 (GLI1) gene (HH-pathway target gene) in biopsy specimens

154 HCA characterized by fusion of the INHBE and GLI1 genes and activation of sonic hedgehog pathway.

155 ed transcription of TNF-alpha, TGF-beta, and GLI1 genes.

156 GLI1, GLI2 and GLI3 form a family of transcription facto

157 r of several important genes, including SHH, GLI1, GLI2, and PDGFA, previously linked to the maintena

158 ned agonist (SAG) increased levels of Ptch1, Gli1, Gli2, Gli3, Hes1 and Hes5, and stimulated the form

159 (controls), and searched for mutation(s) in GLI1, GLI2, GLI3, SUFU, and SOX10.

160 (CD24 and CD133), components of Shh pathway (Gli1, Gli2, Patched1/2, and Smoothened), Gli targets (Bc

161 ment of vemurafenib-resistant cells with the GLI1/GLI2 inhibitor Gant61 led to decreased invasion of

162 ased expression of the transcription factors GLI1/GLI2 was independent of canonical Hh signaling and

163 glioma-associated oncogene homolog 1 and 2 (GLI1/GLI2) compared with naive cells.

164 In contrast, loss-of-function mutations in GLI1 have remained elusive, maintaining enigmatic the ro

165 We saw increased Gli1 (hedgehog readout) in postnatal Six2creFrs2alphaKO

166 To confirm the role of Gli1, hedgehog inhibitor cyclopamine, Gli1 siRNA and Gli

167 repair of demyelinated lesions by inhibiting Gli1, identifying a new therapeutic avenue for the treat

168 This newly identified GLI1/IL-6 axis is active in fibroblasts, a known source

169 Indeed, inhibition of Gli1 improves the functional outcome in a relapsing/remi

170 tic genes can be inhibited by overexpressing GLI1 in AA-sensitive cells.

171 s and demonstrate a regulatory role for Ptc1-Gli1 in adult neural circuit integrity of the brain.

172 Overexpression of GLI1 in AML cells led to increased AKT phosphorylation a

173 ively, these results define a novel role for GLI1 in carcinogenesis acting as a downstream effector o

174 , we demonstrate that IKKbeta phosphorylates GLI1 in DLBCL.

175 Inhibition of GLI1 in human lung SCC cell lines suppressed tumor cell

176 is of the mechanisms revealed a key role for GLI1 in maintaining the levels of activated STAT3 throug

177 The role of GLI1 in pancreatic tumor initiation promoting the progre

178 issue repair and highlight the importance of GLI1 in regulation of the pancreatic microenvironment du

179 By genetically demarcating cells expressing Gli1 in response to Hedgehog (Hh) signaling, we discover

180 ese progenitors acquire theca lineage marker Gli1 in response to paracrine signals Desert hedgehog (D

181 We identified two putative binding sites for GLI1 in the AKT1 promoter region and confirmed their fun

182 a novel and tumor-specific role for aberrant Gli1 in the regulation of the S-phase checkpoint that su

183 biological role of the transcription factor GLI1 in the regulation of tumor growth is well establish

184 Inhibition of Gli1 in tumor cells induced replication stress-mediated

185 cription factor glioma-associated protein 1 (GLI1) in AA-treated cells is the underlying mechanism co

186 We conclude that GLI1 inactivation is associated with a phenotypic spectr

187 However, mechanisms underlying GLI1-increased activity in DLBCL are poorly characterize

188 Correspondingly, Gli1 inhibition affected the expression of Bid and the a

189 These results indicated that GLI1 inhibition alone, but not combined inhibition, is s

190 ed drug sensitivity, which was attenuated by GLI1 inhibition.

191 The GLI1(+) interstitial cells eventually develop into two c

192 tion of the Hh effector transcription factor Gli1 is a poor prognostic factor in this disease setting

193 Furthermore, the SHH target gene Gli1 is preferentially expressed in subepithelial fibrob

194 -cycling NSCs express Gli2 and Gli3, whereas Gli1 is restricted ventrally and all three genes are dow

195 pression of hedgehog molecules, particularly Gli1, is common in cancers of many tissues and is respon

196 ating or deleting these residues facilitated GLI1-ITCH interaction and decreased the protective effec

197 Here, we directly tested the role of Gli1(+) kidney pericytes in the maintenance of peritubul

198 To address this issue, we crossed the gli1 knock-out (GKO) animal with cre-dependent pancreati

199 GLI1-KO mice phenocopied the SULF2-KO, showing delayed r

200 darinaparsin ameliorated fibrosis in WT and Gli1-KO mice, it was not effective in conditional Gli2-K

201 former response was verified by increases in Gli1-LacZ activity and Gli1 mRNA expression.

202 interfering RNA-mediated knockdown of SMO or GLI1 led to decreased cell proliferation.

203 ctivity, whereas IKKbeta silencing decreased GLI1 levels and transcriptional activity.

204 ineage-tracing experiments revealed that the Gli1 lineage cells that originate in utero eventually po

205 tes with the proximal promoter region of the Gli1 locus, and does so in a manner that can be reversed

206 ctor in the Hh-Gli pathway, and that PCAF or GLI1 loss reduces the levels of H3K9 acetylation on Hh t

207 Thus Gli1 marks mesenchymal progenitors responsible for both

208 Here, we demonstrate that Gli1 marks perivascular MSC-like cells that substantiall

209 s weak in N/TERT-GLI1 cells, indicating that GLI1 may activate anti-apoptotic mechanisms(s) independe

210 ategy that targets the PI3K-mTOR pathway and GLI1 may lead to effective outcomes for PI3K pathway-dep

211 rstanding the poorly elucidated mechanism of Gli1-mediated transcription allows to identify novel mol

212 complex through SMAD4 RNAi depletion impairs GLI1-mediated transcription of BCL2 and cellular surviva

213 The ectopic expression of NANOG inhibits GLI1-mediated transcriptional responses in a dose-depend

214 etwork regulated by the transcription factor GLI1 mediating KRAS-induced carcinogenesis.

215 es: Wt1(+) cells indigenous to the ovary and Gli1(+) mesenchymal cells that migrate from the mesoneph

216 ate tracing in two murine models of BMF that Gli1(+) mesenchymal stromal cells (MSCs) are recruited f

217 that bone marrow myofibroblasts derive from Gli1(+) mesenchymal stromal cells and that a Gli inhibit

218 l, arsenic trioxide and itraconazole reduced GLI1 messenger RNA levels by 75% from baseline (P < .001

219 Moreover, primary T-ALL cases with high GLI1 messenger RNA levels, but not those with low or und

220 Conversely, inhibition of GLI1 mimics AA treatments, leading to decreased tumor gr

221 dgehog inhibitor cyclopamine, Gli1 siRNA and Gli1(-/-) mouse embryonic fibroblasts (MEFs) were used.

222 ified by increases in Gli1-LacZ activity and Gli1 mRNA expression.

223 ibitors that act by destabilizing the CRD-BP-GLI1 mRNA interaction.

224 the physical interaction between CRD-BP and GLI1 mRNA so as to find inhibitors for such interaction.

225 is of human lung cancer datasets showed that GLI1 mRNA was highly expressed in human lung SCC and por

226 s: Ki67 tumor proliferation and HH activity (GLI1 mRNA).

227 of the Wnt/beta-catenin signaling, binds to GLI1 mRNA, stabilizes it, and consequently upregulates i

228 abilization of glioma-associated oncogene 1 (GLI1) mRNA by coding region determinant binding protein

229 These findings implicate perivascular Gli1(+) MSC-like cells as a major cellular origin of org

230 etic fate tracing indicates that adventitial Gli1(+) MSC-like cells migrate into the media and neoint

231 ssion by expression of the GLI3 repressor in GLI1+ myofibroblast progenitors limited kidney fibrosis.

232 easured by immunofluorescence staining; Shh, Gli1, Ngn1, and BMP4 proteins were measured by western-b

233 By contrast, neither the expression of GLI1 nor apoptosis in response to Ara-C treatment of AML

234 urther analysis reveals that IKBKE regulates GLI1 nuclear translocation and promotes the reactivation

235 In addition, using the Gli1 null allele and a Gli3 repressor allele, we reveal

236 e developing molars showed changes in Runx2, Gli1, Numb, and Notch expression in the dental pulp cell

237 GLI1 oncogene has been implicated in the pathobiology of

238 Genetic Inducible Fate Mapping to mark adult Gli1- or Smooth muscle actin-expressing cells and follow

239 The previously unreported Msi2-Shh-Gli1 pathway adds to the growing understanding of the co

240 mice, we observed increased distance between Gli1(+) pericytes and endothelial cells after AKI (mean+

241 l Stem Cell, Kramann et al. (2016) show that Gli1+ perivascular cells in the outermost vessel layer a

242 Interestingly, in this model, GLI1 played a tumor-protective function, where survival

243 haracterized by non-steroidogenic GATA4- and Gli1-positive cells within the steroidogenic cortex, whi

244 Hh-responsive Gli1-positive interstitial cells underwent 11-fold proli

245 ates from a specific pool of hedgehog-active Gli1+ progenitor cells that differentiate and produce mi

246 ranslocation of NFATc1, which then binds the GLI1 promoter and represses its transcription.

247 ARP-T1 was found to directly bind to the GLI1 promoter, thus inhibiting GLI1 expression, and loss

248 ibitor of Hh signal transduction by inducing GLI1 protein degradation in vitro and in vivo.

249 a novel Hh pathway component stabilizing the GLI1 protein in a demethylase-independent manner.

250 1 demonstrated that the corresponding mutant GLI1 protein is fabricated by patient cells and becomes

251 IKKbeta activation increased GLI1 protein levels and transcriptional activity, wherea

252 enesis (VEGFR2, p-ERK, p-PLCr1/2), hedgehog (Gli1, Ptch1, SMO), and mTOR (pS6K1) signaling pathways t

253 Inhibition of Gli1 reduced UGT1As, eliminated drug glucuronides, and r

254 lls revealed an unexpected mechanism whereby Gli1 regulates ATR-mediated Chk1 phosphorylation by tran

255 the design and analysis of trials targeting GLI1-related pathways.

256 ng root development in the AP and HERS using Gli1 reporter mice.

257 ation, indicating that NFATc1 activation and GLI1 repression require the generation of reactive oxyge

258 only, a surrounding population of Ptch1 and Gli1 responding cells is maintained in signaling centers

259 e subcellular distribution and activation of GLI1 resulting in the modulation of epithelial mesenchym

260 nstream of SMO to phosphorylate and activate GLI1, resulting in maximal DNA binding and transcription

261 Deletion of a single allele of Gli1 results in improper stromal remodeling and perduran

262 by genetic or pharmacological inhibition of GLI1, revealing a potential strategy to overcome drug re

263 The smallest region of GLI1 RNA binding to CRD-BP was mapped to nucleotides (nt

264 the two stem-loops are important for CRD-BP-GLI1 RNA binding.

265 rget region for the inhibition of the CRD-BP-GLI1 RNA interaction and Hedgehog signaling pathway.

266 was found to be effective in blocking CRD-BP-GLI1 RNA interaction.

267 istinct stem-loops present in nts 320-380 of GLI1 RNA, was found to be effective in blocking CRD-BP-G

268 d KH2 domain are critical for the binding of GLI1 RNA.

269 Our findings suggest that Ptc1-Gli1 signaling deregulation resulting abnormal loss of G

270 Furthermore, we found that deficits of Ptc1-Gli1 signaling induced NSCs/GPCs into asymmetric divisio

271 In this study, we found that a BMP-Smad4-SHH-Gli1 signaling network may provide a niche supporting tr

272 amyloid plaques in AD brains, affected Ptc1-Gli1 signaling, we treated GPCs with Abeta peptides, we

273 ole of Gli1, hedgehog inhibitor cyclopamine, Gli1 siRNA and Gli1(-/-) mouse embryonic fibroblasts (ME

274 However, in normal fibroblasts, Gli1 siRNAs showed no significant changes in CPT-induced

275 and CYCLIN D1, are dependent upon the intact GLI1-SMAD-PCAF complex for transcriptional activation.

276 Activation of the TGFbeta pathway induces GLI1-SMAD4 complex binding to the BCL2 promoter whereas

277 creased the protective effect of TNFalpha on GLI1 stability.

278 dependent phosphorylation sites that mediate GLI1 stability.

279 2 promoter and are required for TGFbeta- and GLI1-stimulated gene expression.

280 r shrinkage, which may be owing to transient GLI1 suppression with sequential dosing.

281 ously, we identified schlafen 4 (Slfn4) as a GLI1 target gene and myeloid differentiation factor that

282 6, mIL-8, Mcp-1, and M-csf (Csf1), as direct GLI1 target genes potentially mediating this phenomenon.

283 Our results demonstrate that Gli1 that is upregulated at the tumor-stroma intersectio

284 addition, we found that PCAF interacts with GLI1, the downstream effector in the Hh-Gli pathway, and

285 tion of either site abrogated the ability of Gli1 to activate Has2 promoter in a cell-based assay.

286 factors are required for the recruitment of GLI1 to the BCL2 promoter.

287 guingly, loss of EPHA2 induces activation of GLI1 transcription factor and hedgehog signaling that fu

288 ement binding protein that in turn represses gli1 transcription.

289 Finally, we determined whether this novel GLI1 transcriptional pathway could regulate other TGFbet

290 cell growth during tissue regeneration, as a GLI1 transcriptional target.

291 Gli2, but not Gli1, transcriptionally regulated the expression levels

292 Importantly, reduced expression of Shh and Gli1 was also observed in these mice, demonstrating dimi

293 significantly higher than in testis, whereas GLI1 was significantly higher in testis than ovaries.

294 mediated nuclear factor-kappaB activity with GLI1, we identified a crosstalk between these 2 pathways

295 identified FAS and FASL as direct targets of GLI1, whereas GKO/KPC mice showed lower levels of this l

296 n of the sonic hedgehog transcription factor Gli1, which elevated the UDP glucuronsyltransferase UGT1

297 t not Abeta1-40 significantly decreased Ptc1-Gli1, while Shh itself was elevated in hippocampal NSCs/

298 tc1) and its associated transcription factor Gli1 with genesis of specific neuronal progeny.

299 ssociated genes (including Pten, Tpd52, Myc, Gli1, Xiap, and Bbc3/PUMA).

300 one B as the first small molecule binding to Gli1 zinc finger and impairing Gli1 activity by interfer