ライフサイエンスコーパス: TTF-1

1 TTF-1 activates transcription of target genes, including

2 TTF-1 binds to and activates the transcription of genes

3 TTF-1 directly interacts with the conserved DNA binding

4 TTF-1 dose-dependently activated alpha(7) transcription

5 TTF-1 interacted with SRC-1 and CBP in vitro.

6 TTF-1 is a critical regulator of transcription for the s

7 TTF-1 is acetylated by nuclear receptor coactivators inc

8 TTF-1 is amplified in lung cancers, suggesting that it i

9 TTF-1 is an enhancer of class I promoter activity; Pax-8

10 TTF-1 is an essential transcription factor required for

11 TTF-1 knockdown and overexpression studies showed that T

12 TTF-1 protein synergistically stimulated the hSP-B promo

13 TTF-1 transactivated SP-C-chloramphenicol acetyltransfer

14 TTF-1 was subsequently found in lung tissue, where it re

15 ification of thyroid transcription factor 1 (TTF-1 or NKX2-1) biochemical activity as a transcription

16 addition to thyroid transcription factor 1 (TTF-1) and hepatocyte nuclear factor 3alpha (HNF-3alpha)

17 Thyroid transcription factor 1 (TTF-1) is a 42 kDa homeodomain (HD) containing the tissu

18 Thyroid transcription factor 1 (TTF-1) is a homeodomain-containing nuclear transcription

19 hat PPFP and thyroid transcription factor 1 (TTF-1) physically interact, and that these transcription

20 s (RARs) and thyroid transcription factor 1 (TTF-1) stimulated SP-B gene expression in respiratory ep

21 d binding of thyroid transcription factor 1 (TTF-1) to an upstream response element (TTF-1-binding el

22 15, and that thyroid transcription factor 1 (TTF-1) transactivates promoter activity.

23 Thyroid transcription factor 1 (TTF-1) was identified for its critical role in thyroid-s

24 orylation of thyroid transcription factor 1 (TTF-1), expressed selectively in developing lung epithel

25 Thyroid transcription factor 1 (TTF-1), hepatocyte nuclear factor 3alpha (HNF-3alpha), a

26 tion factor, thyroid transcription factor 1 (TTF-1), in rat FRTL-5 thyrocytes.

27 dependent on thyroid transcription factor 1 (TTF-1).

28 Thyroid transcription factor 1 (TTF-1/Nkx-2.1) plays a critical role in lung morphogenes

29 f endogenous thyroid transcription factor 1 (TTF-1/Nkx2.1) to the miR-29ab1 promoter in HFL type II c

30 I (NFI) and thyroid transcription factor 1 (TTF-1; also called Nkx2.1).

31 the role of thyroid transcription factor-1 (TTF-1) and hepatocyte nuclear factor 3 (HNF3) in the dow

32 d that three thyroid transcription factor-1 (TTF-1) binding elements (TBEs) located within a 255 base

33 old, whereas thyroid transcription factor-1 (TTF-1) increased the activity of these constructs 12-18-

34 Thyroid transcription factor-1 (TTF-1) is expressed in respiratory epithelial cells, whe

35 Thyroid transcription factor-1 (TTF-1), a member of the Nkx2 family of homeodomain-conta

36 rs including thyroid transcription factor-1 (TTF-1).

37 pressing rat thyroid transcription factor-1 (TTF-1).

38 -1 (TSEP-1); thyroid transcription factor-1 (TTF-1); and Pax-8.

39 Thyroid transcription factor-1 (TTF-1/Nkx-2.1) is required for formation of the lung and

40 A binding of thyroid transcription factor-1 (TTF-1/Nkx2.1), a master regulator of lung development.

41 s including thyroid transcription factors 1 (TTF-1; refs 4,5) and 2 (TTF-2; refs 6,7) and Pax8 are ab

42 TSEP-1, TTF-1, and/or Pax-8 are involved in TSH/cAMP-induced neg

43 Only Gli1 induces Nkx2.1/TTF-1(+) ventral forebrain neurons.

44 at-beta, stimulated the phosphorylation of a TTF-1-flag fusion protein 6-7-fold in H441 pulmonary ade

45 Co-transfection with a TTF-1 expression vector moderately transactivated the -1

46 GATA-6, but not GATA-5, markedly activated TTF-1 gene transcription in HeLa cells.

47 In addition, TTF-1 interacted directly with RARalpha and TIF2 in the

48 Although TTF-1 is amplified in primary human lung cancers, it inh

49 ure, nuclear localization of CBP, SRC-1, and TTF-1 increased in ductular epithelium in association wi

50 taining demonstrated that both HNF-3beta and TTF-1 were detected in bronchiolar and alveolar type II

51 ts of cotransactivating with both GATA-6 and TTF-1 expression constructs were additive.

52 TF-1, supporting the concept that GATA-6 and TTF-1 might directly interact to influence target gene e

53 miR-29ab1 promoter in HFL type II cells, and TTF-1 increased miR-29ab1 promoter-driven luciferase act

54 ustered retinoic acid-responsive element and TTF-1 binding sites were identified in the enhancer regi

55 n which retinoic acid-responsive element and TTF-1 DNA binding sites overlap.

56 Protein-protein interactions between Erm and TTF-1 were demonstrated by mammalian two-hybrid assays a

57 REB, CREM, ATF-1, ATF-2 as well as c-Jun and TTF-1.

58 NFATc3 and TTF-1 activated the Sftpd promoter, synergized transcrip

59 roid-specific transcription factors Pax8 and TTF-1, leading to expression of the thyroid-specific tar

60 f H441 cells greatly stimulated both RAR and TTF-1 DNA binding to the hSP-B enhancer region in H441 c

61 RAR and TTF-1 synergistically stimulated the hSP-B promoter in H

62 In addition, RAR and TTF-1 were colocalized in mouse bronchiolar and alveolar

63 In the present studies, RAR and TTF-1 were colocalized in the nucleus of H441 cells.

64 protein-protein interactions between RAR and TTF-1 were demonstrated by the glutathione S-transferase

65 moter activity suggesting that Sp1, Sp3, and TTF-1 and HNF-3alpha interact cooperatively with SP-B pr

66 P-ribose) polymerases (PARP-2 and PARP-1) as TTF-1 interacting proteins that influence its transcript

67 sites, which were specifically identified as TTF-1 binding sites by gel retardation and antibody supe

68 factor NK2 homeobox 1 (NKX2-1; also known as TTF-1).

69 e findings identify miR-29 family members as TTF-1-driven mediators of SP-A expression and type II ce

70 Interactions between TTF-1 and GATA-6 required the amino-terminal and zinc fi

71 Likewise, mutation of the GBS blocked TTF-1 activation of the SP-A promoter.

72 nM) caused a time-dependent decrease in both TTF-1 and HNF3 in nuclear extracts and accumulation of b

73 protein-DNA interactions within the -320 bp TTF-1-responsive region of the SP-C gene, were identifie

74 nding sites was synergistically activated by TTF-1 and GATA6, and we show that TTF-1 and GATA6 physic

75 nding sites completely blocked activation by TTF-1, indicating both sites are required for TTF stimul

76 m is regulated in a combinatorial fashion by TTF-1, GATA6, and Foxa2.

77 activation of surfactant B gene promoters by TTF-1 in vitro.

78 ports the first miRNAs directly regulated by TTF-1 and clarifies how TTF-1 controls HMGA2 expression.

79 gene expression, which also is regulated by TTF-1 and Pax-8 in the thyroid, is decreased simultaneou

80 In lung cancers, TTF-1 displays seemingly paradoxical activities.

81 Transgenic mice carrying TTF-1 DNA-binding site mutations completely abolish expr

82 In MLE cells, TTF-1-luciferase reporter constructs were activated by c

83 supershift assays were used to characterize TTF-1, HNF-3 (TGT3), and Sp1/Sp3 binding sites.

84 ed expression after co-transfection with CMV-TTF-1 in HeLa and MLE cells.

85 d SUMOylated BEND3 stabilizes NoRC component TTF-1-interacting protein 5 via association with ubiquit

86 -197 to -158 segment contained two consensus TTF-1 sites, which were specifically identified as TTF-1

87 s TTF-1 expression and controls constitutive TTF-1 levels.

88 Conversely, TTF-1 counters epithelial to mesenchymal transition in c

89 that the ability of pioglitazone to decrease TTF-1 expression contributes to its pro-adipogenic actio

90 TSH/cAMP decreases TTF-1 complex formation with the silencer, thereby decre

91 f TTF-1(+) lung cancer cells (designated EDM-TTF-1(+)) displayed an anti-angiogenic activity in the e

92 stimulating factor (GM-CSF) level in the EDM-TTF-1(+) conferred the antiangiogenic activities.

93 r 1 (TTF-1) to an upstream response element (TTF-1-binding element [TBE]).

94 Expression vectors encoding TTF-1 and the catalytic subunit of protein kinase A (PKA

95 II cells decreased DNA binding of endogenous TTF-1, blocked cAMP stimulation of surfactant proteins,

96 RAR DBD greatly enhanced TTF-1 homeodomain DNA binding activity to a hSP-B enhanc

97 activity but that Erm significantly enhanced TTF-1-mediated SP-C transcription.

98 g in its hyperacetylation, further enhancing TTF-1 DNA-binding and transcriptional activity.

99 hermore, in cells that lack TTF-1, exogenous TTF-1 expression dampened the inhibitory effect of TGF-b

100 mice with the highest transgene expression, TTF-1 caused severe inflammation, pulmonary fibrosis, re

101 the essential pulmonary transcription factor TTF-1 and suppressed by Egr-1 during pulmonary developme

102 issue-specific thyroid transcription factor (TTF-1) DNA-binding sites.

103 ortant lung-restricted transcription factors TTF-1, GATA6, and Foxa2.

104 of lung developmental transcription factors (TTF-1, NKX2-8, and PAX9) that we recently discovered as

105 Finally, TTF-1 knockdown conferred human lung cancer cells resist

106 at acetylation is an important mechanism for TTF-1 activity.

107 65 bp) and specifically to binding sites for TTF-1 and HNF3, which act as cell-specific enhancers of

108 The thyroid transcription factor 1 gene (TTF-1 or NKX2-1) is essential to lung development; howev

109 nfluences the transcription of target genes, TTF-1, and surfactant proteins.

110 irectly regulated by TTF-1 and clarifies how TTF-1 controls HMGA2 expression.

111 each of the HNF-3 binding sites in the human TTF-1 gene inhibited the binding of MLE cell nuclear pro

112 TA-6 strongly enhanced activity of the human TTF-1 gene promoter in vitro.

113 tructs containing the 5' region of the human TTF-1 gene were transfected into immortalized mouse lung

114 ar extracts, thyroid transcription factor I (TTF-1) homeodomain, hepatic nuclear factor (HNF)-3beta,

115 We recently identified TTF-1 in rat parafollicular C cells and parathyroid cell

116 [32P]orthophosphate into immunoprecipitated TTF-1 protein also was markedly increased by cyclic AMP

117 By contrast, the levels of immunoreactive TTF-1 protein were similar in nuclear extracts of contro

118 nd steroid receptor coactivator-1 (SRC-1) in TTF-1 regulation of SP-A expression.

119 The changes in TTF-1 inversely alter CaSR gene and calcitonin gene expr

120 Furthermore, alpha(7) was not detected in TTF-1-null mice and markedly increased in TTF-1-overexpr

121 abolished the cyclic AMP-induced increase in TTF-1 DNA-binding activity.

122 in TTF-1-null mice and markedly increased in TTF-1-overexpressing mice.

123 In cultured type II cells, cAMP increased TTF-1 acetylation.

124 mbers of the HNF-3/forkhead family influence TTF-1 gene expression, deletion constructs containing th

125 miR-200 antagonists inhibited TTF-1 and surfactant proteins and up-regulated TGF-beta2

126 ed incorporation of [32P]orthophosphate into TTF-1 protein; however, the DNA binding activity of TTF-

127 Furthermore, in cells that lack TTF-1, exogenous TTF-1 expression dampened the inhibitor

128 This suggests that cAMP-mediated TTF-1 phosphorylation facilitates interaction with CBP a

129 S. pombe Reb1p is 24-29% identical to mouse TTF-1 (transcription termination factor-1) and Saccharom

130 the VEGF promoter element contains multiple TTF-1-responsive sequences.

131 ses epigenetic changes that permit access of TTF-1 and NF-kappaB to the SP-A promoter.

132 alpha. and HFH-8 inhibited the activation of TTF-1-luciferase by HNF-3beta.

133 w miRNAs influence the oncogenic activity of TTF-1 and the role of TTF-1 in cholesterol metabolism.

134 The activity of TTF-1 is influenced by its interactions with other trans

135 rovides a mechanism by which the activity of TTF-1 on target genes is modulated.

136 , increasing the transcriptional activity of TTF-1 on the SP-C promoter.

137 rotein; however, the DNA binding activity of TTF-1 was decreased in nuclear extracts of TPA-treated t

138 Moreover, the transcriptional activity of TTF-1 was suppressed by cotransfection of a dominant neg

139 occludin, which represents another avenue of TTF-1-mediated metastasis suppression.

140 to the metastasis-critical signaling axis of TTF-1 to HMGA2, we used both reverse and forward strateg

141 ouse SP-A promoter is mediated by binding of TTF-1 at four distinct cis-active sites located in the 5

142 Binding of TTF-1 to GATA-6 required the homeodomain of TTF-1, but o

143 romoter activity, RNA levels, and binding of TTF-1 to these genes are, respectively, decreased or inc

144 dent and is mediated by increased binding of TTF-1/Nkx2.1 and NF-kappaB to a critical response elemen

145 the cohort of patients with coactivation of TTF-1 and NKX2-8 pathways appears to be resistant to sta

146 or prognosis associated with coactivation of TTF-1 and NKX2-8 was validated in 2 other independent cl

147 Coexpression of TTF-1 and PKA-cat increased fusion gene expression 3-4-f

148 RP-2 interacted via the C-terminal domain of TTF-1.

149 at TAZ binds to the NH(2)-terminal domain of TTF-1.

150 ither carboxyl- or amino-terminal domains of TTF-1.

151 Surprisingly, the EDM of TTF-1(+) lung cancer cells (designated EDM-TTF-1(+)) dis

152 the region -399 to -256 influence effects of TTF-1 on SP-A promoter activity.

153 Increased expression of TTF-1 altered alveolarization and caused chronic pulmona

154 In human lung cancer, the expression of TTF-1 and GM-CSF exhibits a statistically significant an

155 least in part by altering the expression of TTF-1 and its potential targets.

156 e expression without affecting expression of TTF-1 in doxycycline-treated double-transgenic mice.

157 sion 3-4-fold as compared with expression of TTF-1 in the absence of PKA-cat.

158 -like morphology and decreased expression of TTF-1, aquaporin-5 (AQP5), zonula occludens-1 (ZO-1), an

159 Increased expression of TTF-1, however, caused dose-dependent alterations in pos

160 s is critical for constitutive expression of TTF-1; TG decreases NFI binding to the NFI elements in a

161 GA2) mediates the antimetastatic function of TTF-1.

162 d the combined N terminus and homeodomain of TTF-1 were critical for this interaction.

163 TTF-1 to GATA-6 required the homeodomain of TTF-1, but optimal interactions with GATA-6 required the

164 We suggest that a PKA-induced increase of TTF-1 phosphorylation and TBE binding activity mediates

165 gene expression in a process independent of TTF-1.

166 ion occurred through a direct interaction of TTF-1 with the OCLN and CLDN1 promoters.

167 In contrast, higher expression levels of TTF-1 disrupted alveolar septation, causing emphysema.

168 Sites and levels of TTF-1 expression vary during lung morphogenesis and foll

169 er involves cytoplasmic trapping and loss of TTF-1 and HNF3 from the nucleus.

170 Modulation of TTF-1 gene expression by members of the HNF-3/forkhead f

171 A substitution mutation of TTF-1 (Thr9 two head right arrow Ala) abolished phosphor

172 Mutation of TTF-1-binding sites (TBE) 1, 3, and 4 in combination mar

173 Modest overexpression of TTF-1 caused type II cell hyperplasia and increased the

174 hibited the PKA-dependent phosphorylation of TTF-1 in vitro.

175 Phosphorylation of TTF-1 mediates PKA-dependent activation of surfactant pr

176 In the presence of TTF-1, TAZ synergistically activated the expression of m

177 was associated with increased recruitment of TTF-1, NF-kappaB, PCAF, and CBP, as well as enhanced ace

178 cAMP and IL-1 stimulated the recruitment of TTF-1, p65, CBP, and steroid receptor coactivator 1 to t

179 within 1.15 kb of the 5' flanking region of TTF-1.

180 on, demonstrating that precise regulation of TTF-1 is critical for homeostasis in the postnatal lung.

181 be under a direct and positive regulation of TTF-1.

182 -33a) is under direct positive regulation of TTF-1.

183 TG mediates the repression of TTF-1 gene expression by decreasing NFI RNA and protein

184 oncogenic activity of TTF-1 and the role of TTF-1 in cholesterol metabolism.

185 In order to determine the role of TTF-1 in lung formation, transgenic mice were generated

186 ocated 96-101 base pairs from major start of TTF-1 gene transcription.

187 phosphorylation site at the NH2 terminus of TTF-1.

188 AZ mRNA and protein overlapped with those of TTF-1 and surfactant protein C (SP-C) in the respiratory

189 Through both gain- and loss-of-TTF-1 expression strategies, we show that TTF-1 positive

190 of the mouse WNT7b promoter containing only TTF-1 binding sites was synergistically activated by TTF

191 cell line with negligible endogenous NFI or TTF-1 activity.

192 nced hSP-A promoter activation by SRC-1 plus TTF-1.

193 ining 1.1 kb of the mouse alpha(7) promoter, TTF-1, and Egr-1.

194 , HNF-3 beta, HFH-4; the homeodomain protein TTF-1; and N-myc, are all expressed in the developing pu

195 Surfactant proteins, TTF-1, and aquaporin 5 expression were conditionally ind

196 with MLE cell nuclear extracts and purified TTF-1 homeodomain protein.

197 ncation/deletion studies showed that the RAR-TTF-1 interaction was mediated through the RAR DNA bindi

198 rt a model in which RAR/retinoid X receptor, TTF-1, and coactivators (p160 members and CBP) form an e

199 rt a model in which RAR/retinoid X receptor, TTF-1, coactivators, and CBP form a transcription activa

200 Recombinant TTF-1 was phosphorylated by purified PKA catalytic subun

201 Adenoviral E1A overexpression reduced TTF-1 +/- SRC-1 induction of SP-A promoter activity, sug

202 The unifying theory regarding TTF-1 is that it exhibits both pro-oncogenic and anti-me

203 order to test whether GATA factors regulated TTF-1 gene transcription, GATA-5 and -6 expression vecto

204 ts, at bp -264 to -153, positively regulates TTF-1 expression and controls constitutive TTF-1 levels.

205 Ligands or signals regulating TTF-1 levels in lung or neural tissue are unknown.

206 Surprisingly, pioglitazone repressed TTF-1 expression in PPFP-expressing thyrocytes.

207 lung-specific transcription pathways (SFTPB, TTF-1), cell adhesion, and signal transduction.

208 tathionine transferase pull-down assay shows TTF-1 direct interaction with the SRC-1 histone acetyltr

209 g adenocarcinomas, we observed that silenced TTF-1 expression down-regulated occludin, which we suppo

210 ) transcription in vitro by binding specific TTF-1 regulatory elements in the mouse alpha(7) promoter

211 Here, we demonstrate that TTF-1 transactivated the expression of the epithelial ti

212 g cotransfection assays, we demonstrate that TTF-1, GATA6, and Foxa2 can trans-activate the WNT7b pro

213 atin immunoprecipitation, we determined that TTF-1 binds to the promoter of SREBF2, the host gene of

214 n summary, this study provides evidence that TTF-1 may reprogram lung cancer secreted proteome into a

215 We found that TTF-1 DNA binding activity was increased in nuclear extr

216 We hypothesize that TTF-1 similarly coordinates Ca2+-dependent gene expressi

217 Our data indicate that TTF-1 interacts with PPFP to inhibit the pro-adipogenic

218 tivated by TTF-1 and GATA6, and we show that TTF-1 and GATA6 physically interact in vivo.

219 In this report, we show that TTF-1 is present in the parafollicular C cells of multip

220 of-TTF-1 expression strategies, we show that TTF-1 positively regulates vascular endothelial growth f

221 kdown and overexpression studies showed that TTF-1 inhibits PPFP target gene expression and impairs a

222 rophoretic mobility shift assays showed that TTF-1, GATA6, and Foxa2 can bind to a specific subset of

223 Collectively, these data suggest that TTF-1 transcriptionally regulates occludin, which repres

224 of HMGA2 without the 3'-UTR, suggesting that TTF-1 keeps the prometastasis gene HMGA2 in check via up

225 ulating cholesterol metabolism suggests that TTF-1 may be a modulator of cholesterol homeostasis in t

226 We show, therefore, that TTF-1 is a Ca2+-modulated transcription factor that coor

227 The TTF-1-dependent upregulation of VEGF was moderately sens

228 The TTF-1-induced VEGF upregulation occurs in both compartme

229 ugh the RAR DNA binding domain (DBD) and the TTF-1 homeodomain.

230 at the lysine residue at position 182 in the TTF-1 HD is acetylated in respiratory epithelial cells.

231 ected mutagenesis of the GATA element in the TTF-1 promoter region inhibited transactivation by GATA-

232 Coactivation of the TTF-1 and NKX2-8 pathways identified a cluster of patien

233 ancer cell lines showing coactivation of the TTF-1 and NKX2-8 pathways were shown to exhibit resistan

234 Site-specific mutagenesis of either of the TTF-1 binding sites completely blocked activation by TTF

235 identified elements in the 5' region of the TTF-1 gene that bound MLE cell nuclear proteins consiste

236 ther increase the secreted VEGF level of the TTF-1(+) lung cancer cells.

237 anscription by suppressing expression of the TTF-1, TTF-2, and Pax-8 genes.

238 However, mutation of the TTF-1-binding sites alone or in combination decreased GA

239 roteins and inhibited transactivation of the TTF-1-luciferase constructs after cotransfection with HN

240 t the region between bp -264 and -153 on the TTF-1 promoter contains two nuclear factor I (NFI) eleme

241 cell nuclear extracts reduced binding to the TTF-1 binding element upstream of SP-A gene.

242 translation and directly interacted with the TTF-1-binding element in the sp-C promoter.

243 f cytokeratin 18, E-cadherin, thyroglobulin, TTF-1 and Pax-8 proteins.

244 TAZ binds to TTF-1, increasing the transcriptional activity of TTF-1

245 endent gene expression in all cells in which TTF-1 and the CaSR are expressed, i.e., parathyroid cell

246 ion, transgenic mice were generated in which TTF-1 was expressed in respiratory epithelial cells of w

247 ation of favorable prognosis associated with TTF-1(+) lung adenocarcinomas.

248 GATA-6 is co-expressed with TTF-1 in the respiratory epithelium in vivo and respirat

249 ells (MLE-15 cells), being co-expressed with TTF-1 mRNA.

250 -C gene transcription when co-expressed with TTF-1, supporting the concept that GATA-6 and TTF-1 migh

251 e lung epithelial cell (MLE15) extracts with TTF-1 and was identified by mass spectrometry.

252 munoprecipitated from the cell extracts with TTF-1.

253 PARP-2 and PARP-1 interact with TTF-1 and regulate the expression of surfactant protein

254 e hypothesis that NFI isoforms interact with TTF-1 to differentially regulate SP-C transcription, we

255 thesis that NFI family members interact with TTF-1 to regulate type II cell function.

256 Although GATA-4 also interacted with TTF-1 in two-hybrid assays, GATA-4 was not as active as

257 trated that the TAZ directly interacted with TTF-1.

258 tion, which results from an interaction with TTF-1.

259 Cotransfection of NFI family members with TTF-1 induced synergistic activation of the SP-C promote

260 GST-GATA-6 directly co-precipitated with TTF-1 after in vitro translation and directly interacted

261 rgistic activation of the sp-C promoter with TTF-1.

262 in the activation of the sp-C promoter with TTF-1.

263 ns, CBP and SRC-1 acted synergistically with TTF-1 to increase SP-A promoter activity.

264 ter, binding and acting synergistically with TTF-1.

265 expression vectors were co-transfected with TTF-1 luciferase expression vector.