ライフサイエンスコーパス: RAR alpha

1 RAR alpha can interact with ER-binding sites, but this o

2 RAR alpha strongly interacts with SMRT and can repress t

3 RAR alpha, RXR alpha, and Mrp2 RNA levels were determine

4 RAR-alpha in nuclear extracts bound both 9c-RA and t-RA

5 RAR-alpha protein is rapidly synthesized in response to

6 RAR-alpha, RAR-beta, and RAR-gamma mRNAs were expressed

7 RARs alpha, beta, and gamma and RXR-alpha were expressed

8 e segment: a short (S)-form type, PML exon 3 RAR alpha exon 3; a long (L)-form type, PML exon 6 RAR a

9 e (V)-form type, variably deleted PML exon 6 RAR alpha exon 3.

10 pha exon 3; a long (L)-form type, PML exon 6 RAR alpha exon 3; or a variable (V)-form type, variably

11 rmal skin ranged from 75% (RXR-beta) to 96% (RAR-alpha) in SCC and from 37% (RAR-gamma) to 68% (RXR-b

12 A RAR alpha agonist displayed 100 times greater potency th

13 AGN194301, a RAR alpha-specific antagonist, suppressed the SCD expres

14 Furthermore, a RAR alpha antagonist completely abolished the growth inh

15 e first human clinical study with TAC-101, a RAR-alpha selective retinoid.

16 synthetic retinoids to selectively activate RAR alpha or beta signaling in this model, we demonstrat

17 ression is negatively regulated by activated RAR alpha.

18 cation and characterization of high-affinity RAR alpha/beta selective agonists with limited RAR gamma

19 ions involving retinoic acid receptor alpha (RAR alpha) and its fusion partners including promyelocyt

20 leukemia (PML)/retinoic acid receptor alpha (RAR alpha) and RAR alpha/PML fusion cDNAs to the early m

21 ovel series of retinoic acid receptor alpha (RAR alpha) antagonists, 1-5, are described.

22 er effect depended on the RA receptor alpha (RAR alpha) but did not require Smad3, despite the fact t

23 involving the retinoic acid receptor alpha (RAR alpha) gene fused to one of several distinct loci, i

24 some 15 to the retinoic acid receptor alpha (RAR alpha) gene on chromosome 17, creating two novel fus

25 s fused to the retinoic acid receptor-alpha (RAR alpha) gene, yielding two classes of chimeric protei

26 Retinoic acid receptor-alpha (RAR alpha) is a known estrogen target gene in breast can

27 Retinoic-acid receptor-alpha (RAR-alpha) and peroxisome proliferator-activated recepto

28 ovel synthetic retinoic acid receptor-alpha (RAR-alpha) selective retinoid, in patients with advanced

29 or a defective retinoic acid receptor-alpha (RAR-alpha), ATRA is unable to reduce levels of TGF-beta-

30 tant mice for RXR alpha(-/-), RXR alpha(-/-)/RAR alpha(-/-), and RAR alpha(-/-)/RAR gamma(-/-), confi

31 ular responses elicited by treatment with an RAR alpha-selective ligand plus RXR-selective ligand.

32 ective RAR(beta)(/gamma) ligands, but not an RAR(alpha)-selective agonist, mimicked the action of at-

33 receptor pan-agonist; and CD336 = Am580, an RAR-alpha agonist) caused significant decreases in numbe

34 RXR alpha and RAR alpha enhanced growth inhibition by all-trans-retino

35 ng two novel fusion genes, PML-RAR alpha and RAR alpha-PML.

36 pha(-/-), RXR alpha(-/-)/RAR alpha(-/-), and RAR alpha(-/-)/RAR gamma(-/-), confirming that RA transa

37 retinoic acid receptor alpha (RAR alpha) and RAR alpha/PML fusion cDNAs to the early myeloid compartm

38 also binds ER beta, TR beta, PPAR gamma, and RAR alpha.

39 Mrp2 and RAR alpha:RXR alpha protein abundance and activity were

40 ance the transcription activated by RARs and RAR alpha-RXR alpha heterodimers under RA concentrations

41 expresses RAR-gamma (approximately 87%) and RAR-alpha makes up the remainder.

42 at patients with ER-negative tumors that are RAR alpha positive may be candidates for retinoid therap

43 noic acid (RA) induced gene transcription at RAR alpha.

44 o significant relationship was found between RAR alpha-labeled cells and clinical stage (P = 0.139),

45 ctions and examined the relationship between RAR alpha and estrogen receptor protein expression by co

46 Overexpression of both RAR-alpha and RXR-alpha resulted in a level of growth in

47 ligand-independent manner and equally bound RAR alpha, but not RXR alpha, and only in the presence o

48 d that the rat Mrp2 promoter is activated by RAR alpha:RXR alpha, and that interleukin 1 beta (IL-1 b

49 ting that conversion can also be mediated by RAR alpha 2.

50 t cancer cells and suggest that low cellular RAR alpha may regulate the signaling switch from RAR-med

51 ts, we investigated the effects of combining RAR alpha/beta selective agonists with various cytotoxic

52 e in the PML gene that is linked to a common RAR alpha gene segment: a short (S)-form type, PML exon

53 trast, the down-regulation of PKC diminished RAR alpha protein half-life and markedly inhibited AF-2-

54 resence of mRNAs initiated from two distinct RAR alpha gene promoters, alpha1 and alpha2.

55 cDNAs of cell surface antigen CD7 and either RAR alpha, RAR beta, RAR gamma, or RXR alpha.

56 the transgene relative to that of endogenous RAR alpha revealed that downregulation of RAR alpha is i

57 s of wild type foregut shows that endogenous RAR alpha activity is required to maintain overall RA si

58 of RXR ligands with RAR ligands (especially RAR alpha agonists) and/or antiestrogens may have utilit

59 d to retinoid treatment because they express RAR alpha, whereas ER-negative breast cancer cell lines

60 R-negative cell line, Hs578T, also expressed RAR alpha (approximately 23 fmol/mg) and was sensitive t

61 All seven cell lines expressed RAR-alpha and RAR-gamma, and four cell lines showed some

62 us adenocarcinomas are capable of expressing RAR alpha and estrogen receptor despite high histologica

63 In MDA-MB-231 clones stably expressing RAR alpha, both RARbeta induction and growth inhibition

64 T-47D, which expressed approximately 35 fmol RAR alpha/mg total protein (9-cis retinoic acid; EC50, a

65 dependent manner, providing a novel role for RAR alpha that is independent of its classic role.

66 exhibited varying degrees of selectivity for RAR alpha relative to RAR beta/gamma, with compound 5 be

67 an affinity-purified antiserum specific for RAR alpha and a monoclonal antibody recognizing the full

68 human PMNs contain constitutive message for RAR-alpha but little or no protein.

69 T lymphocytes expressed mRNA and protein for RAR-alpha, RXR-alpha, and RXR-beta.

70 ia (APL) produces the reciprocal fusion gene RAR alpha-PML.

71 with the retinoic acid receptor alpha gene (RAR alpha).

72 APL-specific fusion proteins with identical RAR alpha moieties.

73 These findings implicate RAR alpha as an essential component of the ER complex, p

74 iated with cytokine-dependent alterations in RAR alpha:RXR alpha nuclear receptors.

75 The PKC-mediated increase in RAR alpha was due to a 2.5-fold increase in the half-lif

76 ic mice demonstrated 30% to 80% reduction in RAR alpha protein expression in various tissues.

77 ever activation of PKC resulted in increased RAR alpha protein.

78 n protein and, in a similar manner, inhibits RAR alpha target gene expression and myeloid differentia

79 5' PML breaksite cases coded for full-length RAR alpha-PML proteins but RAR alpha2-PML mRNAs from 3'

80 minant RAR alpha 1 isoform leaves too little RAR alpha 2 for RA to inhibit the generation of Th17 cel

81 lly associated with down-regulation of liver RAR alpha:RXR alpha nuclear protein levels and binding t

82 tors for all-trans retinoic acid in mammals, RAR alpha, RAR beta, and RAR gamma, which transduce the

83 to phosphorylation and activation by MAPKs, RAR-alpha was not phosphorylated by the activated ERK2 M

84 s that atRA treatment or adenovirus-mediated RAR-alpha overexpression significantly reduced hepatic f

85 nt, we have ectopically expressed a modified RAR alpha with constitutive activity in the limbs of tra

86 nd have been thought to express little or no RAR alpha.

87 d characterized, on a comparative basis, NPM/RAR alpha transgenic mice (TM) in which the fusion gene

88 hCG-NPM/RAR alpha leukemic cells resembled monoblasts.

89 ved in human APL patients, we found that NPM/RAR alpha and PML/RAR alpha, but not PLZF/RAR alpha leuk

90 Importantly, the NPM/RAR alpha oncoprotein was found to localize in the nucle

91 bstructive cholestasis, would reduce nuclear RAR alpha:RXR alpha levels, and that this would be assoc

92 support the idea that balanced activation of RAR alpha and beta is critical for proper lung bud initi

93 , these findings suggest that alterations of RAR alpha gene are rare and therefore other mechanisms m

94 one that may approximate the conformation of RAR alpha when bound to hormone agonist.

95 The consequence of RAR alpha induction by estrogen was previously unknown.

96 us RAR alpha revealed that downregulation of RAR alpha is important in allowing the chondrogenic phen

97 of RB as a downstream target or effector of RAR alpha and RXR in combination.

98 e breast cancer cell lines for expression of RAR alpha protein and responsiveness to retinoids in gro

99 d transactivation are separable functions of RAR alpha, thus indicating that synthetic retinoids with

100 is promoted by the estrogen-ER induction of RAR alpha.

101 These results indicate the involvement of RAR alpha in the induction of SCD expression by retinoic

102 ncer cell lines due to their lower levels of RAR alpha and RARbeta.

103 low (<10 fmol/mg) or no detectable levels of RAR alpha protein and also did not respond to retinoids

104 ere tested, one (SK-BR-3) had high levels of RAR alpha protein as measured by ligand-binding immunopr

105 ve ZR-75-1 cells that express high levels of RAR alpha.

106 pared with the heterogeneous localization of RAR alpha in cancer cells, there was widespread RAR alph

107 on the differential cellular localization of RAR alpha protein in 16 serous adenocarcinomas originati

108 ells cannot be overcome by overexpression of RAR alpha.

109 tionship was found between the percentage of RAR alpha-positive tumor cells and histological grade, a

110 near relationship between the percentages of RAR alpha- and estrogen receptor-labeled tumor cells as

111 level changed the in vivo phosphorylation of RAR alpha.

112 ferent corepressor interaction properties of RAR alpha, -beta and -gamma are determined by a gating m

113 receptors mediate the observed reduction of RAR alpha by RA, and 3) the block of RA responsiveness i

114 ls in delineating the physiological roles of RAR alpha in development and in the adult animal and may

115 To determine the scope of RAR alpha-containing mRNA expression in APL cells, we te

116 RAR alpha proteins was distinct from that of RAR alpha and established which portion(s) of each X-RAR

117 X-RAR alpha was reduced compared to that of RAR alpha.

118 s abrogated by treatment with antagonists of RAR-alpha or of all the RXRs.

119 included our demonstration that blocking of RAR-alpha with the antagonist Ro 41-5253 completely supp

120 ice that expressed an antisense construct of RAR-alpha lacked or produced very low levels of CD38.

121 and in vivo, is under the direct control of RAR-alpha retinoid receptors.

122 in the 2008 cells, whereas the expression of RAR-alpha and RAR-beta was not observed in any cell line

123 The expression of RAR-alpha and RAR-gamma remains positive in HEC specimen

124 Furthermore, induction of RAR-alpha by RA was impaired in the RA resistant SK-OV3

125 ant SK-OV3 cells expressed reduced levels of RAR-alpha and RXR-alpha.

126 mice contained 50% to 80% reduced levels of RAR-alpha.

127 bly, vertebrates encode three major forms of RARs, alpha, beta, and gamma, and these distinct RAR iso

128 PL-specific oncogenes PML-RAR alpha and PLZF-RAR alpha both bind nuclear corepressors and recruit his

129 our data suggest that PML-RAR alpha and PLZF-RAR alpha cause the high-level expression of cyclin A1 s

130 The PML-RAR alpha and PLZF-RAR alpha fusion oncoproteins function as aberrant trans

131 In cells from PLZF-RAR alpha/RAR alpha-PLZF transgenic mice and cells harbo

132 cells expressing PML-RAR alpha but not PLZF-RAR alpha.

133 RA appears to explain the resistance of PLZF-RAR alpha-related APL to RA and at the same time explain

134 c expression of either PML-RAR alpha or PLZF-RAR alpha in U937 cells, a non-APL myeloid cell line, le

135 acid receptor alpha [PML-RAR alpha] or PLZF-RAR alpha) caused the increased levels of cyclin A1 in t

136 the nucleolus, unlike PML/RAR alpha and PLZF/RAR alpha, thus possibly interfering with the normal fun

137 Similarly, hCG-PLZF/RAR alpha TM displayed a different phenotype where termi

138 with those in hCG-PML/RAR alpha and hCG-PLZF/RAR alpha TM.

139 hese genes in PML/RAR alpha, but not in PLZF/RAR alpha expressing U937 cells.

140 PM/RAR alpha and PML/RAR alpha, but not PLZF/RAR alpha leukemia, was responsive to all-trans retinoic

141 r PML/RAR alpha (retinoid-sensitive) or PLZF/RAR alpha (retinoid-resistant) in U937 cells.

142 Finally, ETO interacted with PLZF/RAR alpha and enhanced its ability to repress through th

143 the promyelocytic leukemia zinc finger PLZFt/RAR alpha fusion protein and, in a similar manner, inhib

144 RXR alpha with promyelocytic leukemia (PML)-RAR alpha resulted in reduced mobility of RXR alpha.

145 PML-RAR alpha mRNA type was determined using reverse transcr

146 Among 221 PML-RAR alpha-positive cases, there were 82 S-form cases (37

147 12 of 20 patients (60%) with the type 5 PML-RAR alpha transcript (intron 3 PML breakpoint) had secon

148 (hCG) gene to direct the expression of a PML-RAR alpha cDNA to the early myeloid cells of transgenic

149 teins (PML-retinoic acid receptor alpha [PML-RAR alpha] or PLZF-RAR alpha) caused the increased level

150 The ectopic expression of either PML-RAR alpha or PLZF-RAR alpha in U937 cells, a non-APL mye

151 ute promyelocytic leukemia (APL) express PML-RAR alpha, the fusion product of t(15;17)(q22;q11.2).

152 retinoic acid (ATRA) in cells expressing PML-RAR alpha but not PLZF-RAR alpha.

153 Transgenic mice expressing PML-RAR alpha develop APL with long latency, low penetrance,

154 n MRP8 PML-RARA mice, the activated FLT3/PML-RAR alpha leukemias were characterized by leukocytosis,

155 , high NQ was associated with short-form PML-RAR alpha (P <.001), but not with white blood cell count

156 In addition to the major fusion gene PML-RAR alpha, the t(15; 17) in acute promyelocytic leukemia

157 ome 17, creating two novel fusion genes, PML-RAR alpha and RAR alpha-PML.

158 Although low-level expression of the hCG-PML-RAR alpha transgene is not sufficient to directly cause

159 Mice expressing the hCG-PML-RAR alpha transgene were found to have altered myeloid d

160 time explains the effectiveness of RA in PML-RAR alpha-positive APL.

161 Addition of ATRA inhibited PML-RAR alpha-induced cyclin A1 promoter activity.

162 APDH) normalized quotient (NQ), that is, PML-RAR alpha mRNA copies divided by glyceraldehyde-3'-phosp

163 ic and molecular data, 32 had the type L PML-RAR alpha transcript (intron 6 PML breakpoint).

164 pha2-PML mRNA expression and the type of PML-RAR alpha mRNA formed by either 5' or 3' breaksites in t

165 action (RT-PCR [qrtPCR]) measurements of PML-RAR alpha mRNA in acute promyelocytic leukemia was retro

166 fication of the S-form or L-form type of PML-RAR alpha mRNA, per se, does not predict clinical outcom

167 sults indicate that qrtPCR monitoring of PML-RAR alpha NQ can identify patients at high risk of relap

168 The APL-specific oncogenes PML-RAR alpha and PLZF-RAR alpha both bind nuclear corepress

169 mRNA expression in APL cells, we tested PML-RAR alpha-positive APL cells for the presence of mRNAs i

170 Taken together, our data suggest that PML-RAR alpha and PLZF-RAR alpha cause the high-level expres

171 Reporter assays showed that PML-RAR alpha led to activation of the cyclin A1 promoter.

172 nificant relationship exists between the PML-RAR alpha 5 isoform (intron 3 PML genomic breakpoint) an

173 The PML-RAR alpha and PLZF-RAR alpha fusion oncoproteins functio

174 The PML-RAR alpha fusion gene product, which is expressed in vir

175 The PML-RAR alpha fusion protein is central to the pathogenesis

176 The PML-RAR alpha fusion protein of APL renders haemopoietic pro

177 ute promyelocytic leukemia who carry the PML-RAR alpha fusion respond to all-trans retinoic acid and

178 The primary measure was the PML-RAR alpha(GAPDH) normalized quotient (NQ), that is, PML-

179 romyelocytic leukemia (APL) one of three PML-RAR alpha mRNA types is produced, depending on the break

180 xcluded by central pathology review were PML-RAR alpha negative, and notably, none of five of these c

181 To determine whether PML-RAR alpha is sufficient to cause APML in an animal model

182 We evaluated whether PML-RAR alpha mRNA type is associated with distinct pretreat

183 K-ras from its endogenous promoter with PML-RAR alpha to generate a short-latency, highly penetrant

184 Activated FLT3 cooperated with PML-RAR alpha to induce leukemias in 62 to 299 days (median

185 locytic leukemia-retinoic acid receptor (PML-RAR)alpha (PR), the fusion protein that initiates acute

186 locytic leukemia retinoic acid receptor (PML-RAR)alpha transcript, found in approximately 8% of adult

187 c leukemia-retinoic acid receptor alpha (PML-RAR-alpha) oncoprotein.

188 ncofusion proteins, such as AML1-ETO and PML-RAR-alpha, involves the targeting of histone deacetylase

189 merase-chain-reaction (RT-PCR) assay for PML-RAR-alpha fusion transcripts, and Western blot analysis

190 ts who initially tested positive for the PML-RAR-alpha fusion transcript by the RT-PCR assay later te

191 rthermore, the induced expression of the PML-RAR-alpha oncoprotein increased the expression of cell s

192 ease by promoting the destruction of the PML-RAR-alpha oncoprotein.

193 activity observed after induction of the PML-RAR-alpha oncoprotein.

194 PML/RAR alpha expression is linked to leukemogenesis and to

195 atients, we found that NPM/RAR alpha and PML/RAR alpha, but not PLZF/RAR alpha leukemia, was responsi

196 s of a protein that selectively degrades PML/RAR alpha, and that interferons may regulate PML/RAR alp

197 ated by the ectopic expression of either PML/RAR alpha (retinoid-sensitive) or PLZF/RAR alpha (retino

198 a observed in these TM with those in hCG-PML/RAR alpha and hCG-PLZF/RAR alpha TM.

199 trasts with what was observed in the hCG-PML/RAR alpha TM model in which the leukemic phase was chara

200 RA strongly up-regulated these genes in PML/RAR alpha, but not in PLZF/RAR alpha expressing U937 cel

201 lytic ribozymes in control cells lacking PML/RAR alpha mRNA yielded no apparent growth or differentia

202 s introduced into the NB4 APL cell line, PML/RAR alpha protein expression is reduced.

203 The precise roles of PML/RAR alpha in triggering leukemia or in causing a maturat

204 these findings indicate that persistent PML/RAR alpha expression is required to maintain basal leuke

205 progenitors and their fusions proteins, PML/RAR alpha and AML1/ETO, measured in patients in clinical

206 alpha, and that interferons may regulate PML/RAR alpha expression.

207 ls using a hammerhead ribozyme to target PML/RAR alpha mRNA in the NB4 APL cell line.

208 o the therapeutic potential of targeting PML/RAR alpha in APL.

209 se of a hammerhead ribozyme that targets PML/RAR alpha expression in APL cells reveals the anti-apopt

210 nslocation product and demonstrates that PML/RAR alpha cleavage is insufficient to overcome the diffe

211 When the PML/RAR alpha cleaving but not the non-catalytic control rib

212 This study explores directly these PML/RAR alpha functions in the growth and differentiation of

213 ukemia (APL) yields a fusion transcript, PML/RAR alpha.

214 und to localize in the nucleolus, unlike PML/RAR alpha and PLZF/RAR alpha, thus possibly interfering

215 te promyelocytic leukemia (APL) yields a PML/RAR-alpha fusion messenger RNA species that can be detec

216 s within intron 3 of PML produce a short PML/RAR-alpha isoform, whereas breakpoints within intron 6 r

217 These observations indicate that potent RAR alpha/beta selective agonists may be of therapeutic

218 ls such that a deficiency of the predominant RAR alpha 1 isoform leaves too little RAR alpha 2 for RA

219 etween ATRA and TGF-beta, whereby a putative RAR-alpha-dependent phosphatase activity limits the leve

220 was to develop retinoic acid receptor (RAR) RAR alpha/beta selective agonists with anticancer effica

221 five chimeric retinoic acid alpha-receptor (RAR alpha) genes (X-RAR alpha) created by chromosomal tr

222 Retinoic acid receptor (RAR) alpha has been shown to play a role in retinoid-ind

223 nscription (STAT) 5b-retinoic acid receptor (RAR) alpha is the fifth fusion protein identified in acu

224 The retinoic acid receptor (RAR) alpha, beta(2), and gamma isotypes each regulate sp

225 on the expression of retinoic acid receptor (RAR) alpha, beta, or gamma.

226 resence of activated retinoic acid receptor (RAR) alpha, whereas motoneurons are formed when RARbeta

227 n (h) ADA3 regulates retinoic acid receptor (RAR) alpha-mediated transactivation.

228 e overexpression of a truncated RA receptor (RAR) alpha cDNA, RARalpha403, with strong RAR dominant n

229 , 4HPR, which neither activates RA receptor (RAR) alpha nor retinoic X receptor alpha was unable to i

230 he antagonist of the retinoic acid receptor (RAR)-alpha (Ro41-5253) abrogated the expression of MUC4

231 a dominant-negative retinoic acid receptor (RAR)-alpha mutant (RARdn) using an inducible Cre-Lox sys

232 on demonstrated that retinoic acid receptor (RAR)-alpha, a transcription factor that controls the exp

233 cytic leukemia (PML)-retinoic acid receptor (RAR)alpha and promyelocytic leukemia zinc finger (PLZF)-

234 he nuclear receptors retinoic acid receptor (RAR)alpha, RARbeta, or RARgamma, it appears that the ret

235 lear receptors: the retinoic acid receptors (RAR alpha, beta, and gamma) and the retinoid X receptors

236 troduced the normal retinoic acid receptors (RAR)-alpha, -beta, and -gamma or retinoid X receptor (RX

237 protein 5 (FABP5), retinoic acid receptors (RAR-alpha, -beta, -gamma), and retinoid X receptors (RXR

238 The expressions of five receptors (RAR-alpha and -gamma and RXR-alpha, -beta, and -gamma) w

239 Retinoic acid receptors (RARs) alpha, beta and gamma are key regulators of embryo

240 Some of the nuclear retinoic acid receptors (RARs) alpha, beta, and gamma and retinoid X receptors (R

241 Retinoic acid receptors (RARs) alpha, beta, and gamma contain retinoic acid respo

242 vitamin D receptor; retinoic acid receptors (RARs) alpha, beta, and gamma; and retinoid X receptors a

243 endent interaction of the nuclear receptors, RAR alpha and RXR alpha, with CLOCK and MOP4.

244 Interleukin (IL)-6 strongly reduced RAR alpha expression levels such that a deficiency of th

245 Renal RAR alpha:RXR alpha and Mrp2 expression were preserved u

246 protein thought to transcriptionally repress RAR alpha target genes and block myeloid differentiation

247 induce the apoptosis of trans-RA-resistant, RAR alpha-deficient MDA-MB-231 cells but had low activit

248 ing cells most probably occurred through RXR-RAR alpha heterodimers that also bound to and activated

249 R-selective retinoids in trans-RA-sensitive, RAR alpha-expressing cells most probably occurred throug

250 of both T-47D and SK-BR-3 cells, suggesting RAR alpha involvement in the process.

251 n ER+ human breast cancer cells and suggests RAR-alpha as the major responsible retinoid receptor.

252 Newly synthesized RAR-alpha modulates production of interleukin-8.

253 receptor expression level demonstrated that RAR alpha and RAR gamma RNA expression was reduced in th

254 We show, on a genome-wide scale, that RAR alpha and ER can co-occupy regulatory regions togeth

255 We now show that RAR alpha is required for efficient estrogen receptor-al

256 These data suggest that RAR alpha is necessary for appropriate response of the R

257 to one of the RARs or RXRs, we conclude that RAR-alpha is involved in retinoid-induced CD38 expressio

258 nventional RT-PCR analysis demonstrated that RAR-alpha and -gamma mRNA were expressed in native human

259 The RAR alpha 1 isoform was not essential for RA-dependent e

260 The RAR alpha gene fuses to variable partners (PML, PLZF, NP

261 he transcriptional repression exerted by the RAR alpha fusion oncoproteins.

262 ha results in fetal ventricular defects, the RAR alpha 1 and RAR beta mutations are apparently nonphe

263 tations in mice in the genes that encode the RAR alpha 1, RAR beta, and RXR alpha retinoic acid recep

264 Consistent with this finding, the RAR alpha antagonist, Ro 41-5253, reduced the level of t

265 ion of RAR beta mutants that have gained the RAR alpha-like corepressor phenotype, i.e., a strong int

266 Transgenic mice harboring the RAR alpha fusion genes develop forms of leukemia that fa

267 % decrease in the bound radioactivity in the RAR alpha fraction was accompanied by a proportional inc

268 e activity was required for elevation in the RAR alpha.

269 ent chromosomal translocations involving the RAR alpha locus on chromosome 17 are the hallmark of acu

270 ere recovered in various combinations of the RAR alpha 1, RAR beta, and RXR alpha gene mutations.

271 physiologic changes and deregulation of the RAR alpha in transgenic mice, which resulted in upregula

272 re weakly active in growth inhibition of the RAR alpha-positive cell lines, they markedly increased t

273 that expressed an antisense construct of the RAR alpha.

274 To determine whether the RAR alpha/beta selective agonists could be additive or s

275 phosphorylation was induced the most by the RAR-alpha (193836), followed by RAR-gamma (194433), but

276 atic carcinoma by RA is mediated through the RAR-alpha signaling pathway, and TGF-beta2 may serve as

277 ty of the agonists is exerted solely through RAR alpha, not RARgamma, which is also expressed in both

278 These compounds bind with high affinity to RAR alpha but were completely inactive in gene transacti

279 d further by ligand addition, in contrast to RAR alpha, which showed no change in mobility when ligan

280 ssion could be mediated by ligand binding to RARs alpha, beta, or gamma, but not to retinoid X recept

281 R beta and RAR gamma and express a truncated RAR alpha.

282 Unlike RAR alpha null mice generated by knockout, our antisense

283 RA reduced the amount of unphosphorylated RAR-alpha, whose activation is necessary for RA-induced

284 the ratio of phosphorylated:unphosphorylated RAR-alpha to predominantly the phosphorylated form.

285 HeLa cells, the inhibition is observed when RAR-alpha and/or RXR-alpha but not RAR-beta or RAR-gamma

286 nt inhibition of growth by RA treatment when RAR-alpha was induced.

287 While RAR alpha, RAR beta, and RAR gamma are expressed in dist

288 alpha in cancer cells, there was widespread RAR alpha immunoreactivity in tumor-infiltrating lymphoc

289 tic agents in human diseases associated with RAR alpha.

290 d molar excess of CRABP I was incubated with RAR alpha extract in the presence of [3H]RA and resolved

291 Thus, X-RAR alpha may interfere with RAR alpha through its aberrant nuclear dynamics, resulti

292 a and established which portion(s) of each X-RAR alpha protein-X, RAR, or both-contributed to its alt

293 ted that the intranuclear mobility of each X-RAR alpha was reduced compared to that of RAR alpha.

294 In addition, the mobility of each X-RAR alpha was reduced further by ligand addition, in con

295 R alpha aberrantly colocalized within each X-RAR alpha; colocalization of RXR alpha with promyelocyti

296 oic acid alpha-receptor (RAR alpha) genes (X-RAR alpha) created by chromosomal translocations or dele

297 Both the reduced baseline mobility of X-RAR alpha and the ligand-induced slowing of X-RAR alpha

298 AR alpha and the ligand-induced slowing of X-RAR alpha could be attributed to the protein interaction

299 intracellular localization of each of the X-RAR alpha proteins was distinct from that of RAR alpha a

300 Thus, X-RAR alpha may interfere with RAR alpha through its aberr