ライフサイエンスコーパス: GLI2

1 h concurrent copy number changes in SUFU and GLI2.

2 anner by activating transcriptional mediator Gli2.

3 x C1 (Foxc1) as a transcriptional partner of Gli2.

4 nd the Hedgehog pathway transcription factor Gli2.

5 diated phosphorylation and ubiquitination of GLI2.

6 endent phosphorylation and ubiquitination of GLI2.

7 aired activation of the transcription factor GLI2.

8 f Miz1 prevents the nuclear translocation of Gli2.

9 1 to the primary cilia together with Smo and Gli2.

10 ral development is to restrain activation of Gli2.

11 regions of Gli3 or the C-terminal region of Gli2.

12 pathway in pancreata of mice overexpressing GLI2.

13 his regulatory mechanism is not exclusive of GLI2.

14 decreased expression of both smoothened and GLI2.

15 d to EMT inducer genes like Zeb2, Notch2 and Gli2.

16 ation of the GLI family transcription factor GLI2.

17 stream pathway members, including CREBBP and GLI2.

18 its physical and functional interaction with Gli2.

19 iated oncogene homolog (Gli)1 1.17-fold, and Gli2 1.66-fold).

20 he GLI2 and GLI3 transcriptional activators (GLI2(A) and GLI3(A)) and repressors (GLI2(R) and GLI3(R)

21 We established previously that GLI2, a Kruppel-like transcription factor that acts down

22 explants was reduced by genetically deleting Gli2, a major transcriptional activator of the Hedgehog

23 GLI2, a mediator of hedgehog signaling pathway, was also

24 ed with an increase in the protein levels of GLI2, a transcription factor that is a major mediator of

25 mouse model in which an activated version of GLI2, a transcriptional mediator of the pathway, is over

26 In addition, Hh-independent GLI2 accumulation at the PC tip in cells from the affect

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

28 However, Gli2 activation is able to fully rescue the Smoothened (

29 PDA lines and patient specimens, and forced GLI2 activation is sufficient to convert classical PDA c

30 s results in AKT activation and noncanonical GLI2 activation with subsequent TGFalpha secretion, acti

31 n in Ankmy2 knockout requires both cilia and Gli2 activation.

32 , suggesting that INTU functions upstream of Gli2 activation.

33 duction of a major mediator of Hh signaling, GLI2 activator (GLI2DeltaN), selectively in stem cells o

34 We provide evidence that increased GLI2 activity is also a consequence of increased FGF sig

35 periments in pluripotent P19 cells show that Gli2 activity is sufficient and required for efficient M

36 expression and that blocking Hh-independent Gli2 activity will inhibit tumor-induced bone destructio

37 esistance was neither mutation-dependent nor Gli2 amplification-dependent, and saridegib was found to

38 ld harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often i

39 The modulation of GLI2, an oncogenic transcription factor commonly upregul

40 es from apoptosis by preventing decreases in Gli2 and Bcl-2 expression that were observed in WT lesio

41 scription is activated by Sp1, Sp3, OSX, and GLI2 and by CpG demethylation.

42 essor genes (PTCH1) and activates oncogenes (GLI2 and CCND2), and represents a target for therapy.

43 quires the orthologous transcription factors Gli2 and Ci, respectively.

44 onstitutive GLI3(R) in the absence of normal Gli2 and Gli3 abrogates neurogenesis.

45 spatial distribution, timing, and dosage of GLI2 and GLI3 activators and repressors.

46 Accordingly, inactivating variants in GLI2 and GLI3 are found in several developmental disorde

47 Gli2 and Gli3 are primary transcriptional regulators tha

48 isruption of IFT122 leads to accumulation of Gli2 and Gli3 at cilia tips while blocking the ciliary l

49 se findings, forced Spop expression promotes Gli2 and Gli3 degradation and Gli3 processing.

50 n-3 (Cul3) ubiquitin ligase complex, targets Gli2 and Gli3 for degradation and negatively regulates H

51 GLI1, GLI2 and GLI3 form a family of transcription factors whi

52 Gli proteins) results in destabilization of Gli2 and Gli3 full-length activators but not of their C-

53 as introducing Sufu into the MEFs stabilizes Gli2 and Gli3 full-length proteins and rescues Gli3 proc

54 fibroblasts (MEFs) can restore the levels of Gli2 and Gli3 full-length proteins, but not those of the

55 c over nuclear localization of Gli2, induces Gli2 and Gli3 processing into repressor forms, and activ

56 Although both GLI2 and GLI3 processing were disrupted in talpid(2) mut

57 alian spinal cord, likely through protecting Gli2 and Gli3 proteins from degradation.

58 light of recent findings that Sufu protects Gli2 and Gli3 proteins from proteasomal degradation.

59 zation results from the reduced formation of Gli2 and Gli3 repressors and early depletion of adenylyl

60 Ablation of Gli2 and Gli3 revealed a minor role for GLI2(R) and litt

61 rovides a new insight into the regulation of Gli2 and Gli3 stability and processing by Sufu and Spop,

62 the neural tube and acts in combination with Gli2 and Gli3 to pattern ventral and intermediate neuron

63 The specific mechanism by which the GLI2 and GLI3 transcriptional activators (GLI2(A) and GL

64 Post-translational processing of GLI2 and GLI3 was aberrant in the developing facial prom

65 In contrast to Gli2 and Gli3, Gli1 is sparse in HSCs and is not increas

66 interneurons are generated in the absence of Gli2 and Gli3, whereas astrocyte partial gliosis results

67 at the majority of slow-cycling NSCs express Gli2 and Gli3, whereas Gli1 is restricted ventrally and

68 e and activating transcriptional regulators, GLI2 and GLI3.

69 Cs, with decreased expression of smoothened, GLI2 and ILK compared with cells transfected with nontar

70 ly activated MEK1 prolonged the half-life of GLI2 and increased its nuclear translocation, accompanie

71 Accordingly, elevated GLI2 and OPN levels predict shortened overall survival o

72 tribute to long-range regulation of FOXF1 by GLI2 and other transcription factors.

73 a ligand, hedgehog pathway proteins, such as GLI2 and smoothened (SMO), translocate from the cell int

74 tions of the Hh pathway transcription factor Gli2 and the Hh target gene cyclin D1 (Ccnd1) were obser

75 nding, resulting in nuclear translocation of Gli2 and transcription of parathyroid hormone-related pe

76 We show that Pax3 synergizes with both Gli2 and Zic1 in transactivating the Myf5 epaxial somite

77 ic Hedgehog (Shh), GLI family zinc finger 2 (Gli2), and Patched1 (Ptch1) genes by directly binding to

78 ponents including Patched-1, Smoothened, and Gli2, and fail to activate the pathway upon stimulation.

79 with abnormal ciliary trafficking of SMO and GLI2, and impaired processing of Gli transcription facto

80 everal important genes, including SHH, GLI1, GLI2, and PDGFA, previously linked to the maintenance an

81 inase S6K1 interacts with and phosphorylates Gli2, and releases Gli2 from SuFu binding, resulting in

82 ) pathway transcriptional effectors GLI1 and GLI2 are expressed in myofibroblast progenitors; however

83 GLI3 and GLI2 are the transcriptional mediators generally utilize

84 We report that the Hh effectors (Gli1 and Gli2) are expressed exclusively in adjacent platelet-der

85 tive in conditional Gli2-KO mice, supporting GLI2 as a direct darinaparsin target.

86 studies identified the transcription factor Gli2 as a key regulator of parathyroid hormone-related p

87 of Hedgehog signaling, a known regulator of GLI2, as manipulation of Hedgehog had no effect on IgM s

88 and of the zinc finger transcription factor Gli2 at the ciliary tip, resulting ultimately in Gli-med

89 d with either smoothened at the cytoplasm or GLI2 at the nucleus in LX-2.

90 quired for Hh-induced enrichment of Kif7 and Gli2 at the tip of the cilium but is dispensable for Gpr

91 re is a significant increase in the level of Gli2 at the tips of cilia of PKA-null cells.

92 Furthermore, simultaneous deletion of Gli2 attenuated the renal cystic disease associated with

93 ng Zinc finger protein 1 (Miz1) as a Smo and Gli2 binding protein that positively regulates Hh signal

94 retic mobility shift assays, we identified a GLI2 binding site within the -334/-296 region of the M-M

95 Increased GLI2 binding to its cognate cis-element, associated with

96 Hh signaling induced GLI2 binding to the Cdk6 promoter and activated Cdk6 exp

97 munoprecipitation assays we demonstrate that GLI2 binds to the IL-6Ralpha promoter and regulates its

98 ogen-activated protein kinase MEK1 modulates GLI2 both at the mRNA and protein level.

99 Gli1 and Gli2 bound to the promoter and repressed ANO1 transcript

100 tion of GLI transcriptional factors (GLI1 or GLI2), but not SMO signaling inhibition, reduces tumor s

101 Myofibroblast-specific deletion of Gli2, but not Gli1, also limited kidney fibrosis, and in

102 Here, we demonstrated that GLI2, but not GLI1, drives myofibroblast cell-cycle prog

103 Gli2, but not Gli1, transcriptionally regulated the expr

104 Furthermore, reduction of GLI2, but not GLI3, decreased the expression of both SOX

105 on sites, indicating that MEK-RSK stabilizes GLI2 by controlling targeting GSK-3beta-mediated phospho

106 Pharmacologic inhibition of Gli1 and Gli2 by GANT61 or genetic inhibition by transient transf

107 evidence that Sonic hedgehog (Shh) activates Gli2 by stimulating its phosphorylation on conserved sit

108 ed only for anterior limb patterning and why GLI2 can compensate for GLI3A in posterior limb patterni

109 at the CCR3-PI3K-AKT signaling modulates the GLI2-CD40L axis, and GLI2 is required for CCR3-PI3K-AKT-

110 Indeed, surviving N/TERT-GLI1 and -GLI2 cells expressed higher levels of the epithelial-to-

111 hereas Bcl2 was strongly increased in N/TERT-GLI2 cells, the level of induction was weak in N/TERT-GL

112 with control and untreated N/TERT-GLI1 and -GLI2 cells, those that survived genotoxic insult formed

113 tion (P < 0.05), increased numbers of portal Gli2(+) cells (P < 0.017) and portal fibrosis.

114 The numbers of Gli2(+) cells also correlated with portal inflammation g

115 ice showed increased Gli2 protein levels and Gli2+ cells in WM, indicating that Sox17 promotes the ge

116 sive (glioma-associated oncogene 2-positive [Gli2]) cells (P = 0.0013).

117 er ear by ATAC-seq that, in combination with Gli2 ChIP-seq, identified inner ear enhancers in the vic

118 We address the roles of Gli2 ciliary localization by replacing endogenous Gli2 w

119 ULK3 and mFu/STK36 in a manner depending on Gli2 ciliary localization.

120 re, cerebellar patterning was normal in both Gli2-cko and Smo-cko mutant mice, where all Shh function

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

122 nd filiform papilla maintenance was shown by Gli2 constitutive activation.

123 GLI family zinc finger 2 (GLI2) coordinates the Hh transcriptional program; howeve

124 overexpressing SOX9 or constitutively active GLI2 could rescue the antagonistic effects of cyclopamin

125 utants, respectively, suggesting the lack of Gli2(DeltaCLR) activation in development.

126 Significantly, Gli2(DeltaCLR) cannot be activated either by pharmacoche

127 Finally, Gli2(DeltaCLR) exhibits strong transcriptional activator

128 calization by replacing endogenous Gli2 with Gli2(DeltaCLR), a Gli2 variant not localizing to the cil

129 The resulting Gli2(DeltaCLRKI) and Gli2(DeltaCLRKI);Gli3 double mutant

130 The resulting Gli2(DeltaCLRKI) and Gli2(DeltaCLRKI);Gli3 double mutants resemble Gli2-null

131 constitutively active Smoothened (SmoM2) or Gli2 (DeltaNGli2) in the adipocyte lineage of postnatal

132 re we show that GLI1 and an active mutant of GLI2 (DeltaNGLI2) promote apoptotic resistance in N/TERT

133 differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG isl

134 unoprecipitation assays, we demonstrate that GLI2 directly binds and regulates the activity of the CD

135 ular mechanisms underlying both TGF-beta and GLI2-driven M-MITF gene repression.

136 region of the M-MITF promoter, critical for GLI2-driven transcriptional repression.

137 irect transcriptional repression of Gli1 and Gli2 effectors of the SHH pathway, through recruitment o

138 Here, we incorporated a Gli2-EGFP allele into 2 different genetic mouse models o

139 Finally, we identified that Gli1 and Gli2 exhibited different functions in the regulation of

140 li3 repressor (Gli3R) downregulated Gli1 and Gli2 expression and induced gammaH2AX, PARP cleavage, ca

141 ingly, in the absence of TGF-beta signaling, Gli2 expression was downregulated in cells, whereas enfo

142 we identified TFII-I as a novel repressor of GLI2 expression.

143 on is associated with an increase in GLI1 or GLI2 expression.

144 se reporter strains for Shh, Ptch1, Gli1 and Gli2-expression and proliferation markers to identify ce

145 In summary, our results show that GLI1 and GLI2 facilitate the propagation of cells with damaged DN

146 Embryos lacking the Shh effector Gli2 fail to produce appropriate midline cell architectu

147 ive form of GSK-3B degrading glioblastoma 2 (GLI2), followed by the decreased expression of both smoo

148 rved in the Axenfeld-Rieger syndrome impairs Gli2-Foxc1 association as well as Ihh function.

149 s with and phosphorylates Gli2, and releases Gli2 from SuFu binding, resulting in nuclear translocati

150 and RNA-sequencing, we report recurrent FHL2-GLI2 fusion genes in 65% (17/26) of SSTs and other GLI2

151 glioglioma (TMEM106B-BRAF), and a novel PAX3-GLI2 fusion in a rhabdomyosarcoma.

152 Expression of the FHL2-GLI2 fusion in vitro leads to the acquisition of phenoty

153 Our results demonstrate that the FHL2-GLI2 fusion is likely the oncogenic driver of SSTs, defi

154 The FHL2-GLI2 fusions result in transcriptomic activation of the

155 riched phosphorylated RNAPII serine 2 in the GLI2 gene body.

156 led to an increase in Wnt8a and decreases in Gli2, Gli3, and Shh RNA levels.

157 onist (SAG) increased levels of Ptch1, Gli1, Gli2, Gli3, Hes1 and Hes5, and stimulated the formation

158 rols), and searched for mutation(s) in GLI1, GLI2, GLI3, SUFU, and SOX10.

159 y protein trafficking, and the regulation of Gli2/Gli3 activators and repressors.

160 at both Dnchc2 and Wdr34 act between Smo and Gli2/Gli3 in the Hh pathway.

161 );Gli3 double mutants resemble Gli2-null and Gli2;Gli3 double mutants, respectively, suggesting the l

162 The transcription factor GLI2 has an important role in the transduction of Hedgeh

163 ring limb AP patterning, a role for GLI3A or GLI2 has not been fully ruled out, nor has it been deter

164 The transcription factors GLI1 and GLI2 have been implicated in both the initiation and pro

165 Conversely, 14-3-3zeta stabilizes Gli2 in breast cancer cells, and Gli2 partners with Smad

166 2 induction by TGFbeta, a known activator of GLI2 in cancer cells.

167 Furthermore, by removing Gli2 in Gli3 temporal conditional knock-outs, we uncover

168 Finally, forced activation of Gli2 in mESCs increased their proliferation rate.

169 ock-outs, we uncovered an essential role for Gli2 in providing the remaining posterior limb patternin

170 ous and non-cell-autonomous requirements for Gli2 in regulation of pituitary progenitor specification

171 f MEK-RSK paralleled higher protein level of GLI2 in several multiple myelomas (MM) cells relative to

172 at expressed a constitutively active form of Gli2 in the Osx-lineage cells.

173 ulation of CD40L by the transcription factor GLI2 in the tumor microenvironment downstream of CCR3 si

174 Pharmacological and genetic inhibition of GLI2 in WM malignant cells resulted in a reduction in Ig

175 Zic2 also co-immunoprecipitates with Gli2, indicating that Zic2 forms complexes with Gli2 to

176 NT61 (a small molecule inhibitor of Gli1 and Gli2) induced autophagy, as determined by immunoblotting

177 t manner and is required for timely onset of Gli2-induced skin tumorigenesis in mice.

178 motes cytosolic over nuclear localization of Gli2, induces Gli2 and Gli3 processing into repressor fo

179 TFII-I overexpression antagonized GLI2 induction by TGFbeta, a known activator of GLI2 in

180 ivators of this family of proteins (Gli1 and Gli2) inhibited the proliferation of p63(+) and CK5(+) b

181 ed a decrease in osteolysis, suggesting that Gli2 inhibition may block TGF-beta propagation of a vici

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

183 SMO variants respond to aPKC-iota/lambda or GLI2 inhibitors that operate downstream of SMO, setting

184 sification, and that disruption of the Foxc1-Gli2 interaction causes skeletal abnormalities observed

185 This work suggests that GLI2 is a regulator of beta-catenin and provides insight

186 ng evidence that the ciliary localization of Gli2 is crucial for cilium-dependent activation of Hedge

187 GLI2 is elevated in basal-like PDA lines and patient spe

188 thway activation is communicated from Smo to Gli2 is not known.

189 signaling modulates the GLI2-CD40L axis, and GLI2 is required for CCR3-PI3K-AKT-mediated regulation o

190 Taken together, our findings suggest that Gli2 is required for TGF-beta to stimulate PTHrP express

191 t tag, expressed high levels of Ptch2, Gli1, Gli2, Jag2 and Dll-1, and lower levels of Notch4 and Hes

192 rescue the reduction in IgM secretion in the GLI2 knockdown group by overexpressing IL-6Ralpha, thus

193 increased CD40L expression, and, conversely, GLI2 knockdown reduced CD40L expression.

194 KO mice, it was not effective in conditional Gli2-KO mice, supporting GLI2 as a direct darinaparsin t

195 and RSK2 failed to augment the half-life of GLI2 lacking GSK-3beta phosphorylation sites, indicating

196 e, the majority of beta-cells down-regulated GLI2 levels, thereby regaining the full differentiation

197 Bromi controls ciliary morphology and proper Gli2 localization within the cilium.

198 isrupted IFT88 localization and Hh-dependent Gli2 localization.

199 he latter was accomplished by triple IHC for gli2+ (marker of Hh signaling), sox-9 (progenitor marker

200 ely, it is suggested with these results that Gli2 may play a novel role in the self-renewal of plurip

201 textual changes of Smad partners from p53 to Gli2 may serve as biomarkers and therapeutic targets of

202 functional significance of this receptor in GLI2-mediated regulation of IgM secretion.

203 pha (gp80) subunit as a downstream target of GLI2 mediating the regulation of IgM secretion.

204 involving the oncogenic transcription factor GLI2 modulating IgM secretion by WM malignant cells.

205 eurons fail to migrate caudally in the mouse Gli2 mutant that lacks the floor plate, suggesting an ev

206 Finally, Gli2, MyoD, and MEF2C form a protein complex, which enha

207 t of a Gli antagonist GANT58, which inhibits Gli2 nuclear translocation and PTHrP expression in tumor

208 li2(DeltaCLRKI);Gli3 double mutants resemble Gli2-null and Gli2;Gli3 double mutants, respectively, su

209 We further show that the action of Gli2 occurs prior to the closure of Rathke' pouch.

210 endent phosphorylation and ubiquitination of GLI2.Oncogene advance online publication, 3 December 201

211 Thus, the GLI2-OPN circuit is a driver of PDA cell plasticity that

212 ncrease in glial cell production, removal of Gli2 or Gli3 does not alter adult SVZ neurogenesis.

213 vent tumor-induced bone destruction, whereas Gli2 overexpression in tumor cells can promote osteolysi

214 Further analysis indicated that GLI2 overexpression induced increased CD40L expression,

215 GLI2 overexpression rescued the cell-cycle effect of dar

216 We show that GLI2 overexpression supported long-term epidermal regene

217 Additionally, GLI2 overexpression was associated with decreased E-cadh

218 resistance-conferring Smoothened mutants and GLI2 overexpression.

219 stabilizes Gli2 in breast cancer cells, and Gli2 partners with Smads to activate PTHrP and promote T

220 and CD133), components of Shh pathway (Gli1, Gli2, Patched1/2, and Smoothened), Gli targets (Bcl-2, X

221 d by cross-talk between Hedgehog/SMO and AKT/GLI2 pathways in stromal fibroblasts.

222 xpansion during fibrosis, and both Gli1- and Gli2-positive cells differentiated into alpha-smooth mus

223 periments suggest that the INR region of the GLI2 promoter is necessary for GLI2 repression.

224 reveal that BRD4 directly occupies GLI1 and GLI2 promoters, with a substantial decrease in engagemen

225 However, the mechanisms controlling GLI2 protein expression and stabilization are incomplete

226 Consistent with this, Gli2 protein expression is downregulated during neural t

227 CNP-Sox17 mice showed increased Gli2 protein levels and Gli2+ cells in WM, indicating th

228 rials, reduced fibrosis through reduction of GLI2 protein levels and subsequent cell-cycle arrest in

229 Furthermore, the Gli2 protein was heterogeneously detected in mESC nuclei

230 accompanied by attenuated ubiquitination of GLI2 protein.

231 r, is expressed in place of the bifunctional GLI2 protein.

232 The expression of Gli2, Ptch1 and Smo was consistently detected in other t

233 differentiation partially through regulating Gli2/PTHrP during endochondral bone development.

234 vators (GLI2(A) and GLI3(A)) and repressors (GLI2(R) and GLI3(R)) carry out SHH signaling has not bee

235 n of Gli2 and Gli3 revealed a minor role for GLI2(R) and little requirement for GLI(A) function in st

236 usion genes in 65% (17/26) of SSTs and other GLI2 rearrangements in additional 15% (4/26) SSTs, none

237 Here, we demonstrate that the Hh effector, Gli2, regulates MyoD expression and associates with MyoD

238 d, suggesting an Hh-independent mechanism of Gli2 regulation.

239 ast cancer cells with a Gli2-repressor gene (Gli2-rep) reduced endogenous and TGF-beta-stimulated PTH

240 Furthermore, mice inoculated with Gli2-Rep-expressing cells exhibited a decrease in osteol

241 We conclude that Gli1 and Gli2 repress ANO1 by a novel mechanism that is independe

242 region of the GLI2 promoter is necessary for GLI2 repression.

243 ing in metastatic breast cancer cells with a Gli2-repressor gene (Gli2-rep) reduced endogenous and TG

244 in cells, whereas enforced overexpression of Gli2 restored PTHrP activity.

245 Knockdown of GLI1 and GLI2 restored sensitivity to vemurafenib-resistant cells

246 ssion of Gli2DeltaN, a constitutively active Gli2, restored Hh pathway activation in Intu-deficient c

247 ls included: c-jun, ERCC1, XPD, XRCC1, Gli1, Gli2, SHH, IHH, GAPDH and alpha-tubulin.

248 Lastly, we show that Shh/Gli2 signaling controls the diencephalic expression of B

249 Hh-Gli2 signaling inhibits not only adipocyte differentiati

250 an important transcriptional partner of Ihh-Gli2 signalling during endochondral ossification, and th

251 ant expression of HPE-associated genes ZIC2, GLI2, SMAD3 and FGFR1 in human neural stem cells.

252 hree probands had rare damaging mutations in GLI2, SOX11, or GPC4, which function in the Hedgehog, BM

253 04), the ductular reaction (i.e., numbers of gli2+/sox9+ cells; P = 0.03 and alpha-SMA+ cells; P = 0.

254 te that MEK-RSK cascade positively regulates GLI2 stabilization and represses its degradation via inh

255 te that MEK-RSK cascade positively regulates GLI2 stabilization and represses its degradation via inh

256 K-ERK cascade, mimicked the effect of MEK on GLI2 stabilization.

257 GANT61 specifically targeted Gli1 and Gli2 substantiated by specific inhibition of (i) direct

258 rong IFT-A mutants, the Shh pathway proteins Gli2, Sufu, and Kif7 localized correctly to cilia tips,

259 y influencing the activity of Smoothened and GLI2, suggesting TB4 as a novel therapeutic target in li

260 malignancies, we identified CD40L as a novel GLI2 target gene in stromal cells.

261 the Hh transcriptional program; however, the GLI2 targets that promote cancer cell proliferation are

262 Re-expression of Krt17 in Gli2(tg); Krt17(-/-) keratinocytes induces select Th1 ch

263 cific transcription factors such as Elk1 and Gli2 that are downstream of M9-induced signaling pathway

264 ey revealed key roles for the Sp members and GLI2 that possibly cooperate to activate Bril when the p

265 We find that Gli2, the major Hedgehog pathway transcriptional effecto

266 Gli2, the primary effector of Hedgehog signaling, locali

267 echanism reveals that CCL5 signaling induces GLI2 through a PI3K-AKT-IkappaBalpha-p65 pathway and req

268 t signaling, in turn, stabilizes full-length Gli2 through Serine 230, thus enhancing the output of tr

269 2, indicating that Zic2 forms complexes with Gli2 to promote Myf5 expression.

270 tivator but acted cooperatively with Sp1 and GLI2 to synergistically induce the BRIL promoter.

271 inhibition of (i) direct binding of Gli1 and Gli2 to the promoters of target genes HIP1 and BCL-2, (i

272 ax3 strengthens the ability of both Zic1 and Gli2 to transactivate Myf5 in the epaxial somite.

273 We have previously shown that the Gli2 transcription activator critically mediates Ihh fun

274 re not permanently encoded, and identify the GLI2 transcription factor as a master regulator of subty

275 for SUFU in tumorigenesis and maintenance of Gli2 transcription factor circuitries.

276 ll intestinal phenotype, suggesting that the Gli2 transcription factor is the main effector for Hh si

277 cells by expressing an active version of the GLI2 transcription factor, a mediator of the Hh pathway,

278 rane protein Smoothened, but upstream of the Gli2 transcription factor.

279 Moreover, the Shh-induced upregulation of Gli2 transcription prevents Gli activity levels from ada

280 e analyzed its direct targetome and revealed GLI2 transcriptional activation of atypical cadherin and

281 3K-AKT-IkappaBalpha-p65 pathway and requires GLI2 transcriptional activity to modulate IL-6 expressio

282 mechanism activates a noncanonical Hedgehog/GLI2 transcriptional program that promotes cell migratio

283 ntration and thereby modifying SMO-activated GLI2 translocation and GLI1 expression.

284 Mechanistically, GLI2 upregulates expression of the pro-tumorigenic secre

285 Thus, inhibition of Gli2 using GANT58-NPs is a potential therapy to reduce b

286 acing endogenous Gli2 with Gli2(DeltaCLR), a Gli2 variant not localizing to the cilium.

287 expression of the transcription factors GLI1/GLI2 was independent of canonical Hh signaling and was i

288 GLI2 was phosphorylated at Ser230 in an AKT-dependent fa

289 However, the transcriptional induction of Gli2 was unaffected by IPI-926, suggesting the existence

290 as increased whereas Bcl-2 (direct target of Gli2) was downregulated following GANT61 treatment.

291 Finally, GLI1 and GLI2 were upregulated in the kidneys of patients with hi

292 -length and repressor forms of Gli3, but not Gli2, were up-regulated in Spop mutants, and Ihh target

293 O in regulating basal ciliary trafficking of GLI2 when the pathway is off.

294 ion of the Hedgehog (Hh) signaling molecule, Gli2, which in turn increases secretion of important ost

295 n addition, rs11684871 is located in or near GLI2, which may have biologically relevant roles in asth

296 vation of the transcription factors Gli1 and Gli2, which regulate HH target genes.

297 hened (Smo)-dependent activation of Gli1 and Gli2, which transcriptionally regulate target genes.

298 ciliary localization by replacing endogenous Gli2 with Gli2(DeltaCLR), a Gli2 variant not localizing

299 ma-associated oncogene family zinc finger 2 (GLI2)-WNT/beta-catenin signaling crosstalk in human kera

300 nhibition, thus unveiling the direct role of GLI2/WNT crosstalk in cell invasion.