ライフサイエンスコーパス: ERRalpha

1 ERRalpha activated PPARalpha gene expression via direct

2 ERRalpha activation could be a therapeutic strategy for

3 ERRalpha and gamma are critical regulators of cardiac my

4 ERRalpha deficiency reduced activated T-cell numbers in

5 ERRalpha depletion increased basal as well as vascular e

6 ERRalpha fulfills this role by acting directly at genes

7 ERRalpha has also been shown to mediate bone-derived mac

8 ERRalpha is enriched at the promoters of angiogenic, mig

9 ERRalpha is induced in differentiating C2C12 myoblast an

10 ERRalpha levels also correlated with expression of ErbB2

11 ERRalpha mRNA was expressed at levels greater than or si

12 ERRalpha regulated macrophage inflammatory responses by

13 ERRalpha regulates reactive oxygen species production, a

14 ERRalpha showed potential as a biomarker of unfavorable

15 ERRalpha silencing suppressed proliferation and differen

16 ERRalpha upregulated a subset of PGC-1alpha target genes

17 ERRalpha was implicated previously in regulating the gen

18 ERRalpha was recently shown to be a negative prognostic

19 ERRalpha-deficient (Esrra(-/-)) mice showed increased su

20 ERRalpha-deficient ECs exhibit decreased proliferation b

21 including estrogen-related receptor alpha-1 (ERRalpha-1), can activate gene transcription in a consti

22 decreases in PPARG coactivator (PGC)-1alpha, ERRalpha, mitochondrial complexes, and medium chain acyl

23 abolism known to be regulated by PGC-1alpha, ERRalpha, and a second nuclear receptor, PPARalpha.

24 CYP24A1 in the kidney through the PGC-1alpha-ERRalpha pathway.

25 Thus, the PGC-1alpha.ERRalpha interaction is distinct from that of other nucl

26 eceptors, is not required for the PGC-1alpha.ERRalpha interaction.

27 ha is completely dependent on the PGC-1alpha/ERRalpha complex and is further modulated by the action

28 tion in skeletal muscle, with low PGC-1alpha/ERRalpha signalling, and downregulation of oxidative pho

29 s identify the PDK4 gene as a new PGC-1alpha/ERRalpha target and suggest a mechanism whereby PGC-1alp

30 that interferes effectively with PGC-1alpha/ERRalpha-dependent signaling.

31 beta-adrenergic stimulation of a PGC-1alpha/ERRalpha/VEGF axis mediates exercise-induced angiogenesi

32 l and genetic experiments that show that (a) ERRalpha, beta-catenin (beta-cat), and lymphoid enhancer

33 n addition, PGC-1alpha was shown to activate ERRalpha expression.

34 PGC-1alpha was also shown to activate ERRalpha gene expression.

35 drial processes were suppressed in activated ERRalpha(-/-) T cells and T cells treated with two chemi

36 pha, the expression of constitutively active ERRalpha (CA-ERRalpha) was sufficient to enhance metabol

37 Acute ERRalpha inhibition also blocked T-cell growth and proli

38 d Treg--but not Teff--generation after acute ERRalpha inhibition.

39 alpha and estrogen-related receptor 1 alpha (ERRalpha) controls the aggressive properties of prostate

40 Estrogen-related receptors (ERR), ERR alpha (ERRalpha) and ERR gamma (ERRgamma), are orphan nuclear r

41 r receptors estrogen-related receptor alpha (ERRalpha) and ERRgamma are essential transcriptional coo

42 C1beta) and estrogen-related receptor alpha (ERRalpha) are aberrantly expressed in human colon cell l

43 tion factor estrogen-related receptor alpha (ERRalpha) as a potential Parkin target.

44 whereas the estrogen-related receptor alpha (ERRalpha) bound NRRE-1 in extracts prepared from differe

45 ar receptor estrogen-related receptor alpha (ERRalpha) directs the transcription of nuclear genes inv

46 ar receptor estrogen-related receptor alpha (ERRalpha) has been associated with a negative outcome in

47 The estrogen-related receptor alpha (ERRalpha) has been implicated in endocrine-related cance

48 pression of estrogen-related receptor alpha (ERRalpha) has recently been shown to carry negative prog

49 tivator of oestrogen-related receptor alpha (ERRalpha) in brown adipose tissue.

50 logy of the estrogen-related receptor alpha (ERRalpha) in cultured liver cells.

51 Estrogen-related receptor alpha (ERRalpha) is a key regulator of mitochondrial function a

52 The estrogen-related receptor alpha (ERRalpha) is a potential target for activation in the tr

53 The estrogen-related receptor alpha (ERRalpha) is an orphan member of the nuclear receptor su

54 Estrogen-related receptor alpha (ERRalpha) is an orphan nuclear receptor that has been fu

55 The estrogen-related receptor alpha (ERRalpha) is an orphan receptor belonging to the nuclear

56 r receptor, estrogen related receptor alpha (ERRalpha) is required to coordinate the PGC-1alpha -indu

57 1alpha) and estrogen-related receptor alpha (ERRalpha) messenger RNAs.

58 Estrogen-related receptor alpha (ERRalpha) plays a critical role in adult skeletal muscle

59 es estrogen receptor-related receptor alpha (ERRalpha) to regulate osteoclastogenesis.

60 ar receptor estrogen-related receptor alpha (ERRalpha) was identified in a yeast two-hybrid screen of

61 Estrogen-related receptor alpha (ERRalpha) was the first orphan nuclear receptor to be id

62 Estrogen-related receptor alpha (ERRalpha), a member of the nuclear receptor superfamily,

63 of estrogen receptor-related receptor alpha (ERRalpha), a nuclear receptor that cooperates with the t

64 t bound the estrogen-related receptor alpha (ERRalpha), a recently identified component of the PGC-1a

65 servations, estrogen-related receptor alpha (ERRalpha), an orphan nuclear receptor known for its role

66 cluding the estrogen-related receptor alpha (ERRalpha), an orphan nuclear receptor.

67 ing protein estrogen-related receptor alpha (ERRalpha), cap-binding protein 80 (CBP80), and Mediator

68 ar receptor estrogen-related receptor alpha (ERRalpha), implicating ERRalpha as a potential mediator

69 cytes in an estrogen-related receptor alpha (ERRalpha)-dependent manner.

70 1alpha) and estrogen-related receptor alpha (ERRalpha).

71 tivator of oestrogen-related receptor alpha (ERRalpha).

72 nd estrogen receptor-related receptor alpha (ERRalpha); and the expression of key oxidative mitochond

73 ar receptor estrogen-related receptor alpha (ERRalpha; NR3B1) is a key metabolic regulator, but its f

74 an receptor estrogen-related receptor-alpha (ERRalpha) for ERalpha.

75 ar receptor estrogen-related receptor-alpha (ERRalpha) regulates metabolic pathways critical for Teff

76 The estrogen-related receptor-alpha (ERRalpha) regulates mitochondrial biogenesis and glucose

77 led by the estrogen-related receptor alpha1 (ERRalpha) mitochondrial master regulator.

78 lated transcriptional regulator, Bcl3, as an ERRalpha coactivator.

79 e demonstrate that monoamine oxidase B is an ERRalpha target gene whose expression is regulated by PG

80 demonstration of functional activities of an ERRalpha ligand in metabolic animal models.

81 a, PGC-1alpha, and Bcl3 form a complex on an ERRalpha-responsive element within the pyruvate dehydrog

82 To examine this hypothesis, we analyzed ERRalpha and ERalpha in recurrent tamoxifen-resistant br

83 se expression is regulated by PGC-1alpha and ERRalpha and inhibited by the ERRalpha inverse agonist.

84 itation assays confirmed that PGC-1alpha and ERRalpha occupied the mPDK4 promoter in C(2)C(12) myotub

85 ated that Bc13 interacts with PGC-1alpha and ERRalpha, allowing for interaction with both proteins.

86 riptional mechanism involving PGC-1alpha and ERRalpha, and thus may be useful in treating age-associa

87 RF1, NRF2, Tfam, COX-II, PPARdelta, CREB and ERRalpha mRNA and mitochondrial DNA (mtDNA), were signif

88 gether, our results suggest that ERalpha and ERRalpha cooperate to promote endocrine resistance, and

89 umber of genes regulated by both ERalpha and ERRalpha led us to expand our study to the more aggressi

90 Beyond differences in the ERalpha and ERRalpha target gene repertoires, both factors were enga

91 etween estrogen receptor alpha (ERalpha) and ERRalpha initially suggested that these receptors may ha

92 In addition, PGC1alpha and ERRalpha associated at the MYC promoter, supporting the

93 eal KSR1-dependent control of PGC1alpha- and ERRalpha-dependent pathways that are necessary and suffi

94 In contrast, PGC1beta and ERRalpha are not detectable in nontransformed human colo

95 rmore, in fibroblasts null for PPARalpha and ERRalpha, the ability of ERRalpha to activate several PP

96 ates reactive oxygen species production, and ERRalpha knockdown attenuates proliferation and colony-f

97 ensitivity to hormonal blockade therapy, and ERRalpha status may also be predictive of ErbB2-based th

98 ssociated with transcription factors such as ERRalpha, NRF-1, and HNF4alpha, however acetylation and

99 form macromolecular complexes in cells, (b) ERRalpha transcriptional activity is enhanced by beta-ca

100 Mice lacking both ERRalpha and cardiac ERRgamma develop severe bradycardia

101 the endocrine signaling pathways mediated by ERRalpha including association with human disease states

102 PDK4 gene, inhibits the induction of PDK4 by ERRalpha and ERRgamma.

103 esponse element or the MCAD gene promoter by ERRalpha and the related isoform ERRgamma.

104 med in vivo occupancy of the OPN promoter by ERRalpha in HT29 cells, suggesting that OPN is a direct

105 Many of the genes regulated by ERRalpha are known targets for the nuclear receptor PPAR

106 ng genes previously shown to be regulated by ERRalpha or beta-cat.

107 ing transcriptional upregulation of WNT11 by ERRalpha and beta-cat that influences the migratory capa

108 ession of constitutively active ERRalpha (CA-ERRalpha) was sufficient to enhance metabolic capacity b

109 n to synergize with PGC-1alpha to coactivate ERRalpha.

110 Consequently, ERRalpha may potentiate constitutive transcription of es

111 A crucial role for controlling ERRalpha-mediated target gene expression has been ascrib

112 ne occupancy, proangiogenic stimuli decrease ERRalpha expression in ECs.

113 Together, our data document ERRalpha and its mitochondrial program as downstream eff

114 In addition, knocking down endogenous ERRalpha led to reduced OPN expression in HT29 colon can

115 Our work shows that endothelial ERRalpha plays a repressive role in angiogenesis and pot

116 n in the target genes controlled by ERalpha, ERRalpha, and their coactivator AIB1, defining a novel s

117 ght to gain a genome-wide picture of ERalpha-ERRalpha cross-talk using an unbiased microarray approac

118 growth factor receptor, ErbB2, ErbB3, ErbB4, ERRalpha, ERRbeta, and ERRgamma were determined in unsel

119 three ERR subtypes, ECs exclusively express ERRalpha.

120 observed in the nonhepatoma cells expressing ERRalpha and ERRgamma.

121 ctional analyses confirmed a requirement for ERRalpha in tamoxifen- and fulvestrant-resistant MCF-7 c

122 unravel a previously unappreciated role for ERRalpha as a negative regulator of TLR-induced inflamma

123 Our results confirm a role for ERRalpha in breast cancer growth and highlight it as a p

124 ithelial cells displayed higher staining for ERRalpha than normal mucosa, in correlation with elevate

125 Further, ERRalpha was required for the regulation of NF-kappaB si

126 , estrogen-related receptor alpha and gamma (ERRalpha/gamma) in regulating myofibrillar composition,

127 On the one hand, ERRalpha and ERRgamma together are vital for intact card

128 On the other hand, ERRalpha and ERRgamma influence major cardiomyocyte ener

129 Hence, ERRalpha and ERRgamma status may be predictive of sensit

130 RRgamma in breast cancer progression and how ERRalpha and ERRgamma may differentially affect cancer g

131 We show that the major isoform of the human ERRalpha gene, ERRalpha1, can sequence-specifically bind

132 Further investigation identifies ERRalpha as a target gene of SP1.

133 These results identify ERRalpha and ERRgamma as novel PGC-1alpha interacting pr

134 ene-expression analysis was used to identify ERRalpha small-molecule regulators and target genes.

135 To identify ERRalpha-regulated pathways in tissues with high energy

136 class of ERRalpha target genes and implicate ERRalpha and chicken ovalbumin upstream promoter transcr

137 lated receptor alpha (ERRalpha), implicating ERRalpha as a potential mediator of PGC-1alpha action.

138 These results indicate that Phe-329 in ERRalpha-1 and Ala-350 in ERalpha play important roles i

139 oreover, retinal angiogenesis is enhanced in ERRalpha knockout mice compared to that in wild-type mic

140 AM251 induced SUMO-2,3 incorporation in ERRalpha in conjunction with increased protein kinase C

141 Increased ERRalpha levels associated with ER-negative (Fisher's ex

142 In addition, increased ERRalpha expression was linked to reduced overall surviv

143 Further, VEGFA increased ERRalpha recruitment to angiogenesis-associated genes an

144 ells treated with two chemically independent ERRalpha inhibitors or by shRNAi.

145 AMPK activation induced ERRalpha transcript expression in M-ERRalphaWT muscle an

146 rtant regulatory region for estrogen-induced ERRalpha gene expression.

147 tation assays, that 17beta-estradiol induces ERRalpha gene expression in MCF-7 cells through active r

148 satory proliferation observed in DEN-injured ERRalpha-null livers is concomitant with increased nucle

149 In this study, we investigated ERRalpha gene expression and chromatin structural change

150 Known ERRalpha agonists and safe food supplements biochanin A,

151 n NRRE-1, each of which conform to the known ERRalpha monomeric binding consensus.

152 Gene expression profiling of ECs lacking ERRalpha revealed that ERRalpha predominantly acts as a

153 tion of VEGF by PGC-1alpha, and mice lacking ERRalpha also failed to increase vascular density after

154 Here, we show that mice lacking ERRalpha are unable to maintain body temperature when ex

155 M-ERRalpha(-/-) mice exhibited impaired regeneration chara

156 lphaWT) and muscle-specific ERRalpha(-/-) (M-ERRalpha(-/-)) mice after injury by intramuscular cardio

157 ivated protein kinase (AMPK) activation in M-ERRalpha(-/-) muscle.

158 tor (PGC)-1beta, were downregulated in the M-ERRalpha(-/-) muscles at the onset of myogenesis.

159 Adenoviral-mediated ERRalpha overexpression in primary neonatal cardiac myco

160 Moreover, ERRalpha and ERRgamma are candidate targets for therapeu

161 tudy yielded the surprising result that most ERRalpha-regulated genes are unrelated to estrogen signa

162 Our findings highlight a MYC/ERRalpha pathway that contributes to physiological and p

163 athological bone loss by integrating the MYC/ERRalpha axis to drive metabolic reprogramming during os

164 e results of this study suggest that the MYC/ERRalpha pathway should be further explored as a drug ta

165 to a reduced extent in the absence of normal ERRalpha activity.

166 level of expression of many known and novel ERRalpha target genes.

167 In addition to generating a host of novel ERRalpha target genes, this study yielded the surprising

168 diated by proteasomal degradation of nuclear ERRalpha.

169 l for PPARalpha and ERRalpha, the ability of ERRalpha to activate several PPARalpha targets and to in

170 y mediator of the promigratory activities of ERRalpha/beta-cat.

171 gonist inhibits the constitutive activity of ERRalpha in both biochemical and cell-based assays.

172 responsible for the constitutive activity of ERRalpha-1.

173 in increases the transcriptional activity of ERRalpha.

174 so inhibited the transcriptional activity of ERRalpha.

175 irst potent and selective inverse agonist of ERRalpha.

176 To date, no small-molecule agonists of ERRalpha have been identified despite several high-throu

177 Ralpha gene expression via direct binding of ERRalpha to the PPARalpha gene promoter.

178 These results identify a new class of ERRalpha target genes and implicate ERRalpha and chicken

179 HDAC3 coactivation of ERRalpha is mediated by deacetylation of PGC-1alpha and

180 The contribution of ERRalpha in breast cancer progression remains unknown bu

181 Although deletion of ERRalpha is compensated by ERRgamma, combined deletion o

182 CRISPR/Cas9-based deletion of ERRalpha suppressed PGC1alpha regulation of cytoskeletal

183 ompensated by ERRgamma, combined deletion of ERRalpha/beta/gamma abolishes expression of glycogen met

184 not prevent AM251-induced destabilization of ERRalpha protein, whereas proteasome inhibition with MG1

185 ugh direct binding to and destabilization of ERRalpha protein.

186 ndrial physiology through destabilization of ERRalpha.

187 al structure of the ligand-binding domain of ERRalpha with lead compound 29 revealed the presence of

188 of lowing cholesterol and downregulation of ERRalpha as effective adjuvant treatment of NSCLC.

189 owever, metabolic target genes downstream of ERRalpha have not been well defined.

190 eptors could override the positive effect of ERRalpha-1.

191 y provide a rationale for the exploration of ERRalpha as a candidate drug target to treat endocrine-r

192 ed a strategy to knockdown the expression of ERRalpha and gamma in heart after birth (pn-csERRalpha/g

193 I3K/AKT activity regulates the expression of ERRalpha and mitochondrial biogenesis/respiration.

194 Expression of ERRalpha and of its nucleus-encoded mitochondrial target

195 The expression of ERRalpha paralleled NRRE-1 binding activities and MCAD e

196 Functionally, re-expression of ERRalpha sustains cell proliferation by regulating ROS d

197 pecimens (n = 1041), increased expression of ERRalpha was associated with enhanced proliferation and

198 PGC-1alpha also increased the expression of ERRalpha, PPARalpha, and enzymes that support mitochondr

199 negative correlation between expressions of ERRalpha and PTEN in patients with liver cancer.

200 scriptional program and cellular function of ERRalpha in endothelial cells (ECs), a cell type with a

201 kinase 2), were reduced when the function of ERRalpha was inhibited in infected cells.

202 ined its DNA-binding function, indicative of ERRalpha being a target of nuclear proteasomal complexes

203 Promoter analysis, inhibition of ERRalpha activity, and expression and mutation of potent

204 oss of MYC and pharmacological inhibition of ERRalpha attenuated bone loss in a mouse model of osteop

205 Accordingly, pharmacological inhibition of ERRalpha attenuated OVX-induced bone loss in mice.

206 Furthermore, in vivo inhibition of ERRalpha reduced T-cell proliferation and Teff generatio

207 CF-7 cells, with pharmacologic inhibition of ERRalpha sufficient to partly restore sensitivity to ant

208 ERRalpha, and treatment with an inhibitor of ERRalpha impeded anchorage-independent growth.

209 Although stable knockdown of ERRalpha expression in MDA-MB-231 cells had no effect on

210 nregulation of PLA2R1 decreases the level of ERRalpha and of its nucleus-encoded mitochondrial target

211 xically, in clinical studies, high levels of ERRalpha are associated with poor outcomes whereas high

212 sting CD4(+) T cells expressed low levels of ERRalpha protein that increased on activation.

213 Herein we show that global loss of ERRalpha accelerates the development of diethylnitrosami

214 Our work thus shows that global loss of ERRalpha activity promotes hepatocellular carcinoma by i

215 d metabolomics studies revealed that loss of ERRalpha promotes hepatocyte necrosis over apoptosis in

216 In particular, we demonstrate that loss of ERRalpha-dependent regulation of the NF-kappaB inhibitor

217 mplying that pharmacological manipulation of ERRalpha activity may have a significant clinical impact

218 myotubes, and cardiac and skeletal muscle of ERRalpha-/- mice.

219 The cardiac perinatal expression pattern of ERRalpha paralleled that of PGC-1alpha and MCAD.

220 Down-regulation of ERRalpha by AM251 or small interfering RNA led to increa

221 et of AKT, plays a role in the regulation of ERRalpha, independent of PKA signaling.

222 The physiological role of ERRalpha has yet to be established primarily because of

223 However, the role of ERRalpha in cancer in which inflammation acts as a tumor

224 To understand the role of ERRalpha in PGC-1alpha signaling, a parallel approach of

225 veal critical and direct regulatory roles of ERRalpha and ERRgamma in governing both innate and adapt

226 Furthermore, silencing of ERRalpha and beta-cat expression individually or togethe

227 s, suggesting that OPN is a direct target of ERRalpha in colorectal cancer.

228 Upregulation of ERRalpha or ERRgamma is required for the OXPHOS burst in

229 AM251 analogs also have negative impacts on ERRalpha protein levels in a cell-type-dependent manner

230 ary neonatal cardiac myocytes overexpressing ERRalpha.

231 The inverse correlation between PGC1alpha-ERRalpha activity and MYC levels was corroborated in mul

232 gether, these results support that PGC1alpha-ERRalpha functions as a tumor-suppressive transcriptiona

233 vo, identifying suppression of the PGC1alpha-ERRalpha axis leading to perturbed myogenic differentiat

234 ty, and expression and mutation of potential ERRalpha response elements in the proximal promoter of h

235 se activation by phorbol ester also promoted ERRalpha protein loss.

236 Rather, ERRalpha binds PGC-1alpha primarily through a Leu-rich m

237 Rather, ERRalpha broadly affected metabolic gene expression and

238 co-activator-1beta) and the nuclear receptor ERRalpha (estrogen receptor-related receptor alpha), and

239 The orphan nuclear receptor ERRalpha mediated the induction of VEGF by PGC-1alpha, a

240 40 was found to require the nuclear receptor ERRalpha to regulate hexose uptake and mitochondrial pro

241 Estrogen-related receptors ERRalpha and ERRgamma are essential regulators of cardia

242 that the estrogen-related nuclear receptors (ERRalpha and ERRgamma) and their partnered co-factors PG

243 PDK4 gene by the estrogen-related receptors (ERRalpha and ERRgamma).

244 ve found that four orphan/nuclear receptors, ERRalpha-1, EAR-2, COUP-TFI (EAR-3), and RARgamma, bind

245 , ectopic PGC1alpha was sufficient to rescue ERRalpha expression, metabolic capacity, and anchorage-i

246 Consistent with the gene expression results, ERRalpha increased myocyte lipid accumulation and fatty

247 the identification of a potent and selective ERRalpha inverse agonist that interferes effectively wit

248 The discovery of potent and selective ERRalpha modulators and their effect on PGC-1alpha signa

249 S1 may function as a positive element since ERRalpha-1 is expressed, but EAR-2 and RARgamma are only

250 csERRalpha/gamma [postnatal cardiac-specific ERRalpha/gamma]) in mice.

251 Consequently, muscle specific ERRalpha overexpression in mdx mice restored angiogenic

252 wild-type (M-ERRalphaWT) and muscle-specific ERRalpha(-/-) (M-ERRalpha(-/-)) mice after injury by int

253 Surprisingly, ERRalpha is dispensable for the regulation of its classi

254 urther supporting the relevance of targeting ERRalpha with antagonists as anticancer agents.

255 We conclude that ERRalpha is needed for the efficient production of cytom

256 We conclude that ERRalpha serves as a critical nodal point in the regulat

257 Our findings demonstrate that ERRalpha is a key regulator of mitochondrial biogenesis

258 Here, we demonstrate that ERRalpha negatively regulates Toll-like receptor (TLR)-i

259 vitro binding experiments demonstrated that ERRalpha interacts with PGC-1alpha via its activation fu

260 a-null primary fibroblasts demonstrated that ERRalpha is required for PGC-1alpha-mediated activation

261 mmunoprecipitation studies demonstrated that ERRalpha, PGC-1alpha, and Bcl3 form a complex on an ERRa

262 In contrast to the findings that ERRalpha-1 behaves as a positive regulatory factor, thes

263 In this setting, we found that ERRalpha expression is required for the basal level of e

264 eries of NRRE-1 mutant probes indicated that ERRalpha was capable of binding two distinct sites withi

265 ction of the Esrra promoter, indicating that ERRalpha may control gene regulation downstream of the A

266 Here we report that ERRalpha and ERRgamma stimulate the PDK4 gene in hepatom

267 Previous reports that ERRalpha regulates OPN expression in bone prompted us to

268 NativePAGE analysis revealed that ERRalpha formed a approximately 220-kDa multiprotein nuc

269 filing of ECs lacking ERRalpha revealed that ERRalpha predominantly acts as a transcriptional repress

270 Rather, we show that ERRalpha is needed for the high levels of mitochondrial

271 e proximal promoter of human OPN showed that ERRalpha and its obligate co-activator, peroxisome proli

272 Collectively, these results suggest that ERRalpha deficiency during muscle regeneration impairs r

273 The results suggest that ERRalpha may be intractable as a direct target for pharm

274 Recent studies suggest that ERRalpha may indeed promote breast tumor growth.

275 The ERRalpha gene is estrogen-responsive in several mouse ti

276 The ERRalpha-1 mutant F329A lost the transactivation activit

277 Finally, blocking the ERRalpha-controlled mitochondrial program largely inhibi

278 PGC-1alpha and ERRalpha and inhibited by the ERRalpha inverse agonist.

279 In contrast, ectopic expression of the ERRalpha coactivator PGC-1alpha enhanced oxidative metab

280 We mapped the nucleosome positions of the ERRalpha promoter around the MHRE region and found that

281 l transfection experiments revealed that the ERRalpha-1 mutant F329A, like wild-type ERalpha, recogni

282 creased migration could be attributed to the ERRalpha/beta-cat-dependent induction of WNT11.

283 unction by promoting NO* bioactivity through ERRalpha induced expression of eNOS.

284 Thus, ERRalpha is a selective transcriptional regulator of Tef

285 Thus, ERRalpha was the most abundant nuclear receptor in a sub

286 ction of a small interfering RNA directed to ERRalpha into the highly aggressive breast carcinoma MDA

287 alpha with PGC-1alpha in a manner similar to ERRalpha.

288 On the other hand, like wild-type ERRalpha-1, the ERalpha mutant A350F was found to be con

289 ously shown to be an antagonist of wild-type ERRalpha-1.

290 eted Parkin interacts with and ubiquitinates ERRalpha.

291 Unlike ERRalpha, ERRgamma showed potential as a biomarker of fa

292 Additionally, transfection studies using ERRalpha-null primary fibroblasts demonstrated that ERRa

293 These findings validate ERRalpha as a promising therapeutic target in the treatm

294 activators and release of co-repressors when ERRalpha and AP1 bind and ERalpha is tethered to the MHR

295 replication observed in HepG2 cells, whereas ERRalpha and ERRgamma are probably responsible for the m

296 However, whether ERRalpha controls metabolic remodeling during skeletal m

297 n in bone prompted us to investigate whether ERRalpha controls OPN expression in human colorectal can

298 ngs suggest an additional mechanism by which ERRalpha participates in the development and progression

299 isturbed the interactions of PGC-1alpha with ERRalpha and PPARalpha, factors important for mitochondr

300 independent growth required interaction with ERRalpha, and treatment with an inhibitor of ERRalpha im