ライフサイエンスコーパス: AF-2

1 in part by the C-terminal activation helix (AF-2).

2 pendent transcriptional activation function (AF-2).

3 ond located in the carboxyl-terminal region (AF-2).

4 and the second in the COOH-terminal region (AF-2).

5 disc into 5 regions of interest (ROI) (NP-3, AF-2).

6 f coactivators for AR activation function 2 (AF-2).

7 transactivation functional domains, AF-1 and AF-2.

8 this activity requires a functional receptor AF-2.

9 ependent transcriptional activation function AF-2.

10 strengths with and coactivator effects on AR AF-2.

11 T), activate AF-1 preferentially rather than AF-2.

12 f E2-mediated coactivator recruitment to the AF-2.

13 s not suppressed by the physically separated AF-2.

14 uterus of mice with mutations in the ERalpha AF-2.

15 a ligand-dependent transactivation function, AF-2.

16 d both contain activation functions AF-1 and AF-2.

17 activating functional domains (AF), AF-1 and AF-2.

18 Cs (pDC), using mouse lacking either AF-1 or AF-2.

19 ugh two activation functions (AFs): AF-1 and AF-2.

20 through intact AF-1, but not through mutated AF-2.

21 A mutation in the hAR activation function-2 (AF-2) abrogates N-to-C interaction, DNA binding, and tra

22 A conserved AF-2 activation domain located in the hormone-binding do

23 Bon binds via an LxxLL motif to the AF-2 activation domain present in the ligand binding dom

24 ly (p160 coactivators) bind to the conserved AF-2 activation function found in the hormone binding do

25 and -dependent gene transcription (AF-1 and AF-2 (activation functions 1 and 2)).

26 t is still not fully understood how AF-1 and AF-2 activities are regulated cooperatively by ligands.

27 identified as an allosteric modulator of the AF-2 activity and is termed binding function-3 (BF-3).

28 51Y mutation allows weak tamoxifen-dependent AF-2 activity but that this activity is only detectable

29 Furthermore, tamoxifen-dependent AF-2 activity can be detected in the presence of ERalpha

30 h IC(50) approximately 50 microM and inhibit AF-2 activity in cells were detected: three nonsteroidal

31 e inhibitory effect of region F on the HNF-4 AF-2 activity is a unique feature among members of the n

32 the N terminus of the receptor protein, and AF-2 activity is dependent on helix 12 of the C-terminal

33 n the N terminus of the receptor protein and AF-2 activity is dependent on helix 12 of the C-terminal

34 AF-2 activity is mediated by a hormone-dependent interac

35 Whilst AF-2 activity is regulated by estrogen (E2) binding, the

36 lex with estrogen receptor (ER) and enhances AF-2 activity of the receptor.

37 e nuclear receptors, and it is essential for AF-2 activity, but it is not necessary for dimerization

38 es the AF-1 activity of ERalpha, but not the AF-2 activity, suggesting that hMMS19 may be an AF-1-spe

39 s that form BF-3 inhibits AR function and AR AF-2 activity.

40 c nerve glia, axogenesis factor-1 (AF-1) and AF-2, along with ciliary neurotrophic factor.

41 ligand binding domain of ERalpha C terminus (AF-2) and a ligand-independent activation function in th

42 estrogen receptor transactivation function (AF-2) and agonize another (AF-1).

43 50 and DRIP205 functionally link GR AF-1 and AF-2, and represent important mediators of GR transcript

44 ix 12 (H12) in the LBD is a component of the AF-2, and the configuration of H12 is ligand-inducible t

45 RAM-1 binding site in rat TRbeta1 outside of AF-2, as TRAM-1 shows weak ligand-dependent interaction

46 on, since HNF-4 deletion derivatives lacking AF-2 bound TFIIB.

47 p21(Cip1) is agonist dependent and requires AF-2 but not AF-1 or GR dimerization.

48 and enhanced the activity of the C-terminal AF-2 but not the N-terminal AF-1 transactivation domain

49 lpha (ERalpha) activation functions AF-1 and AF-2 classically mediate gene transcription in response

50 tors bind irreversibly to Cys-298 within the AF-2 cleft of TRbeta to disrupt SRC2 association.

51 bilizes the PPARgamma activation function-2 (AF-2) co-activator binding surface and better enhances c

52 in ER transactivation is dependent on the ER AF-2 coactivator binding site, prompting us to examine r

53 he static part of the activation function-2 (AF-2) cofactor binding groove, is sufficient to confer f

54 r E2 or TOT, between the AF-1-containing and AF-2-containing regions of the ER.

55 nal (AF-1-containing) and carboxyl-terminal (AF-2-containing) regions of ER as separate polypeptides

56 Furthermore, we demonstrated that the AF-2 contains an AF-1 suppression function using C-termi

57 ranscriptional activation functions AF-1 and AF-2, controls the transcription of target genes presuma

58 wo FXR transactivation-deficient mutants (an AF-2 deletion and a W469A point mutant) failed to transa

59 to the promoter complex; the second step is AF-2 dependent and entails entry of preinitiation comple

60 nvolves primary HNF-4 activation function 2 (AF-2)-dependent interactions with the TRAP220 subunit of

61 The activation function 2 (AF-2)-dependent recruitment of coactivator is essential

62 increase in receptor activation function-2 (AF-2)-dependent transcriptional activity.

63 h NBD-1 and NBD-2 showed similar ligand- and AF-2-dependent interactions with TR in solution, these t

64 suggesting that the AF-1 is regulated in an AF-2-dependent manner in the male reproductive tract.

65 Estrogen- and antiestrogen-regulated, AF-2-dependent transcriptional activation by purified fu

66 pha protein half-life and markedly inhibited AF-2-dependent transcriptional activity.

67 and ERalpha in the activation helix and the AF-2 dimerization helix indicates that TERP-1 acts predo

68 AF2ER is an AF-2 disrupted estradiol (E2)-insensitive mutant ERalpha

69 indings we hypothesized that the mutation of AF-2 disrupted its ability to suppress AF-1, causing the

70 type ER and a mutant ER that had a defective AF-2 domain (ER TAF-1).

71 sual degree of structural flexibility in the AF-2 domain (helix alpha12).

72 o-terminal FXXLF motif and carboxyl-terminal AF-2 domain (N/C interaction) prevented toxicity and AR

73 The ERR3 AF-2 domain bound GRIP1 in a ligand-independent manner b

74 matin structure was largely dependent on the AF-2 domain for activation.

75 idues 405-419 on delta419 with the conserved AF-2 domain from the vitamin D3 receptor or the estrogen

76 ndings suggest that an important role of the AF-2 domain in the native ER is to mask the activation p

77 demonstrate that p120 interacts with the TR AF-2 domain in the presence of ligand through a 111-amin

78 nesis studies demonstrated that a functional AF-2 domain is essential for toxicity, a finding corrobo

79 receptor (RXR) heterodimer, whereas the VDR AF-2 domain is required for this interaction.

80 DR translocation, demonstrate that an intact AF-2 domain is required for this translocation, and indi

81 This activation required the AF-2 domain of both RXR and RAR.

82 A1, and this interaction was mediated by the AF-2 domain of ER-alpha and two domains of BRCA1, the am

83 The AF-2 domain of ER-alpha was also shown to induce VEGF ge

84 The AF-2 domain of HNF4 is required for this interaction and

85 ormone responsiveness resided near or within AF-2 domain of mCAR.

86 PPARalpha, indicating that the COOH-terminal AF-2 domain of PPAR is not the target of STAT5b inhibiti

87 activator-1 (PGC-1) requires both the intact AF-2 domain of PPARgamma and the LXXLL domain of PGC-1 f

88 Although the AF-2 domain of PPARgamma is absolutely required for PGC-

89 lls that harbor a truncated ligand-dependent AF-2 domain of RARalpha do not demonstrate any changes i

90 tivation (AF)-2 domains, but not the AF-1 or AF-2 domain of RXRalpha, nor CAR's DBD.

91 heterodimer binds directly to DNA, with the AF-2 domain of tethered CAR mediating transcriptional ac

92 Therefore, the AF-2 domain of TR-beta is required for positive and, par

93 n potential of PGC-1alpha requires an intact AF-2 domain of VDR and the LXXLL motif in PGC-1alpha.

94 eins are coactivators that interact with the AF-2 domain of VDR to augment 1,25-dihydroxyvitamin D3-d

95 t chromatin remodeling, but mutations in the AF-2 domain that abolish activity in the native ER also

96 that helix H3 functions in concert with the AF-2 domain to form a transactivation surface for bindin

97 Restoration of ligand-dependent (AF-2 domain) reporter gene activation was achieved by ex

98 RAR in response to ligand displaces the RXR AF-2 domain, allowing RXR ligands to bind and promote th

99 We also show that the AF-2 domain, although inactive at simple promoters on it

100 Mutation of a specific residue in the AF-2 domain, which renders the VDR trancriptionally inac

101 interact on the outer surface of PXR at the AF-2 domain.

102 beta locus within its activation function-2 (AF-2) domain (E457A).

103 The activation function-2 (AF-2) domain of ERalpha and the C-terminal regulatory do

104 re, we found that the activation function-2 (AF-2) domain of the retinoid X receptor interferes with

105 nteraction between the activator function-2 (AF-2) domain of the VDR and C terminus of beta-catenin.

106 terized C-terminal AR activation function-2 (AF-2) domain was critical for strong, ligand-dependent a

107 inding domain, the human ER hormone binding (AF-2) domain, and the VP16 activation domain, functions

108 erved carboxyl-terminal activation function [AF-2] domain of ER-alpha.

109 e results demonstrate directly that AF-1 and AF-2 domains accomplish their transactivation activities

110 two signal input domains (one that binds NR AF-2 domains and one that binds AF-1 domains of some but

111 OPR1 and its longer variant COPR2 target the AF-2 domains of NR but exhibit quantitative differences

112 Truncation of LBD and truncation of AF-2 each abolished hormone-dependent translocation and

113 mice and mice with mutations in the ERalpha AF-2 (ERalphaAF-2(0)) were treated with ICI, estradiol,

114 A ligand-inducible transactivation function (AF-2) exists in the extreme carboxyl terminus of the vit

115 We used an AF-2 flexible region mutant and an AF-2 static region mu

116 ; COPR2, 32.4 kDa), and strict dependence on AF-2 for interaction distinguish COPR1 and COPR2 from th

117 evaluate the physiological role of AF-1 and AF-2 for the tissue-selective function of TAM, we genera

118 st conformation termed activator function-2 (AF-2) for coactivator binding.

119 ndent interactions between the ERalpha D351Y AF-2 function and GRIP1, a representative p160, can be d

120 essing L543A,L544A mutations in H12 disrupts AF-2 function and reverses antagonists such as fulvestra

121 se they were completely dependent on the RXR AF-2 function but independent of both the RXR A/B domain

122 We find that the AF-2 function of ERalpha D351Y lacks detectable tamoxife

123 iated activation by BPA and BPAF was via the AF-2 function of ERalpha, but Zea activated via both the

124 hormone, which was independent of ligand and AF-2 function.

125 vates PPARgamma through the ligand-dependent AF-2 function.

126 nic activity and activated both the AF-1 and AF-2 functions of ERalpha.

127 pha, but Zea activated via both the AF-1 and AF-2 functions.

128 a small compound-binding surface adjacent to AF-2 has been identified as an allosteric modulator of t

129 o post-translational modification on AF-1 or AF-2 has been reported.

130 ty and induces a distinct orientation in the AF-2 helix (H12).

131 The structure shows that the AF-2 helix 12 (H12) rearranges to bind inside the ligand

132 Mutation of the AF-2 helix 12 domain partially inhibits the induction of

133 inforced by the antagonist, which blocks the AF-2 helix from adopting the active position.

134 nding cavity were mapped to helix H3 and the AF-2 helix H12, indicating conformational changes in the

135 The C-terminal helix named alphaAF or AF-2 helix in other nuclear receptors is responsible for

136 Activation of PPARgamma by AJA requires the AF-2 helix of the receptor, suggesting that AJA activate

137 cent to the ligand-dependent transactivation AF-2 helix on the surface of PXR.

138 e most striking of which is a packing of the AF-2 helix onto the LBD adjacent to helices H3 and H4.

139 In this configuration, the AF-2 helix physically excludes the binding of coactivato

140 In each monomer, the AF-2 helix protrudes away from the core domain and spans

141 phenylalanine 435 and a displacement of the AF-2 helix relative to the unliganded structures with li

142 Inhibition of SMRT binding by the AF-2 helix requires specific amino acid sequences and th

143 on of RXR results from a rotation of the RXR AF-2 helix that places it in contact with the RAR coacti

144 from the C2 symmetry, allowing the PPARgamma AF-2 helix to interact with helices 7 and 10 of RXRalpha

145 g domain (LBD) of hPXR, interacting with the AF-2 helix to stabilize the LBD for coactivator binding.

146 ns between the compounds and residues in the AF-2 helix with agonistic activity.

147 repression mechanism that is mediated by the AF-2 helix within the tetramer.

148 the cofactor binding site is occupied by the AF-2 helix, thus preventing ligand-independent activatio

149 trinsic repression activity is masked by the AF-2 helix, which antagonizes SMRT binding.

150 tor's ligand-binding pocket and contacts the AF-2 helix.

151 nding site and only partially stabilizes the AF-2 helix.

152 ctors use a conserved activation function-2 (AF-2) helix 12 mechanism for agonist-induced coactivator

153 act directly with the activation function 2 (AF-2) helix.

154 ins, constitutive AF-1 in the N terminus and AF-2 in the C terminus.

155 functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain.

156 MFA-1 binds with its D ring-facing helix 12 (AF-2) in a manner reminiscent of hormone binding to clas

157 dependent transcriptional activation domain (AF-2) in the C-terminal region of the human vitamin D re

158 vitro, the F domain was found to obscure an AF-2-independent binding site for GRIP1 that did not map

159 titutive, ligand-independent AR activity was AF-2-independent but instead dependent on N-terminal AR

160 for this interaction, which can occur in an AF-2-independent manner.

161 Importantly, the ligand- and AF-2-independent mode of AR activation observed in ADI P

162 The first step involves AF-2-independent recruitment of TFIIB to the promoter co

163 subunit of TRAP/SMCC/Mediator and secondary (AF-2-independent) interactions with TRAP170/RGR1.

164 n A-CDK2 on ER transcriptional activation is AF-2-independent.

165 e-dependent activation domain (named tauc or AF-2) inhibits the ability of RXR-PPARgamma heterodimers

166 two activating functions of HNF-4, AF-1 and AF-2, interact with the N terminus and the N and C termi

167 was selectively impaired in interaction with AF-2-interacting coactivator proteins such as SRC-1 and

168 at interacts simultaneously with the primary AF-2 interaction site.

169 oborated by a genetic screen that identified AF-2 interactors as dominant modifiers of degeneration.

170 AF-2 is composed of two domains with flexible and static

171 We propose that ERalpha lacking AF-2 is constitutively active in the absence of ligand i

172 1 is localized in the N-terminal region, and AF-2 is distributed in the C-terminal ligand-binding dom

173 kably, the full transactivation potential of AF-2 is inhibited by the region spanning residues 371-46

174 cating that the conserved charged residue in AF-2 is not essential for this PGC-1 function.

175 ntexts, the synergistic activity of AF-1 and AF-2 is required for full estradiol (E2)-stimulated acti

176 s a predominant ligand response, whereas RXR AF-2 is required for liganded RAR AF-2 to efficiently tr

177 gand-dependent activation function domain-2 (AF-2) is a primary contributor to the nuclear receptor (

178 ligand-independent AF-1 and ligand-dependent AF-2, located in the A/B and E domains, respectively.

179 To assess the AF-2-mediated AF-1 suppression, we analyzed the transcri

180 activation, a conformational change releases AF-2-mediated repression and transcriptional activation

181 for the ligand-independent activity, whereas AF-2 mediates ligand-dependent PR activation.

182 response requires the DNA binding domain and AF-2 motif of CAR3 and is markedly enhanced by retinoid

183 strong ligand-dependent interaction with an AF-2 mutant of TR (E457A), while SRC-1 fails to interact

184 The AF-2 mutants were not activated by agonists, but surpris

185 en receptor modulators (SERMs) activated the AF-2 mutants.

186 ly coprecipitated the wild-type hVDR and the AF-2 mutants.

187 fy AF-1-dependent estrogenic-genes using the AF-2 mutated knock-in (KI) mouse model, AF2ERKI.

188 ent for 3 wk beginning at age 21 d activated AF-2-mutated ERalpha (AF2ER) and restored expression of

189 e-selective function of TAM, we generated an AF-2-mutated ERalpha knock-in (AF2ERKI) mouse model.

190 ctivation functions using AF-1-truncated and AF-2-mutated ERalpha mutants.

191 In addition, an E457A AF-2 mutation had no effect on the ligand-induced PGC-1

192 These results indicate that the ERalpha AF-2 mutation results in male infertility, suggesting th

193 d for repression, because anti-estrogens and AF-2 mutations impair repression.

194 n domains, ID1 and ID2, whereas the putative AF-2 of ARP1 was required for interaction with CTIP1.

195 lock the transcriptional activation function AF-2 of ER-alpha.

196 t mouse lacking the transactivation function AF-2 of ERalpha (ERalpha-AF2(0)) provided selective loss

197 ng coactivator protein(s) interacts with the AF-2 of PR or TR and mediates transactivation by the lig

198 e conserved COOH-terminal activation domain (AF-2) of ER-alpha.

199 nd estrogen-dependent activation function 2 (AF-2) of ERalpha, AKT increased the activity of only AF-

200 vents the carboxy-terminal activation helix (AF-2) of the receptor from assuming the active conformat

201 p1) is agonist independent, does not require AF-2 or AF-1, but depends on GR dimerization.

202 functions (activation function 1 [AF-1] and AF-2) or receptor dimerization fail to fully inhibit cel

203 -aa deletion in helix 12 of ERalpha, lacking AF-2, or ERalpha(-/-) mice.

204 rated that the activation function 2 domain (AF-2) plays an essential role in VDR transactivation.

205 Several coactivators bind to the AF-2 pocket through conserved LXXLL or FXXLF sequences t

206 is conclusion, we have identified an ERalpha AF-2 point mutant (L540Q) that selectively binds and rec

207 on the opposite side of the protein from the AF-2 region critical for receptor regulation.

208 The AF-2 region in NRs has been thought to play a critical r

209 displaying strong homology to the conserved AF-2 region of nuclear receptors.

210 nteraction also requires the presence of the AF-2 region of RXR to interact with the LXXLL motif of P

211 teraction also requires both helix 1 and the AF-2 region of the TR ligand-binding domain.

212 Coactivator recruitment to the AF-2 region of TR in the presence of T(3) is central to

213 acting with subdomains of NRs other than the AF-2 region, in contrast to SRC-1/TIF2.

214 nd-binding domain/activation function-2 (LBD/AF-2) region (within aa 282-420) of ER-alpha.

215 of which bind to the activation function 2 (AF-2) region of the androgen receptor.

216 sequence, a putative activation function 2 (AF-2) region.

217 ion activities through different mechanisms: AF-2 requires GRIP1 as a coactivator, but AF-1 does not.

218 -terminal transcriptional activation domain, AF-2, retained elevated basal activity, while mutation o

219 c binding pocket on the outer surface at the AF-2 site and fitted comfortably, making interactions wi

220 on the outer surface of the receptor at the AF-2 site and validated by docking studies.

221 e used an AF-2 flexible region mutant and an AF-2 static region mutant.

222 id expressing rat CAR lacking the C-terminal AF-2 subdomain inhibited squalestatin 1-inducible CYP2B1

223 two LXXLL motifs and requires the receptor's AF-2 subdomain.

224 by ERbeta, probably by interacting with the AF-2 surface and blocking the binding of endogenous coac

225 e that E(2)-mediated repression requires the AF-2 surface and the participation of coactivators or ot

226 The requirement of the AF-2 surface for repression is probably due to its capac

227 protein-1 mutant unable to interact with the AF-2 surface is ineffective.

228 e clamp residues Gln-272, and Phe-264 on the AF-2 surface of PXR.

229 vered a role for coactivators binding to the AF-2 surface of the vitamin D receptor (VDR) in its nega

230 The activation function-2 (AF-2) surface in the ligand-binding domain is required f

231 othesized to bind the activation function-2 (AF-2) surface on the exterior of PXR when agonists are c

232 detectable when AF-1 is strong, and AF-1 and AF-2 synergize, or when p160s are overexpressed.

233 tains a transcriptional activation function (AF-2) that mediates hormone-dependent binding of coactiv

234 elical region, termed activation function-2 (AF-2), that forms part of the ligand-binding pocket and

235 ds at the AR surface reveals weak binding at AF-2, the most potent inhibitors bind preferentially to

236 n SPA70 compromises its interaction with the AF-2, thus explaining its antagonism.

237 nRXR alpha) lacking transactivation function AF-2 to differentiated suprabasal keratinocytes in the e

238 hereas RXR AF-2 is required for liganded RAR AF-2 to efficiently trans-activate target genes, and (2)

239 BF-3 remodels the adjacent interaction site AF-2 to weaken coactivator binding.

240 -binding domain linked to the ligand binding/AF-2 trans-activation domain of PPARalpha, indicating th

241 ostructure, but an important pocket near the AF-2 transactivation domain becomes accessible only in s

242 SHP proteins specifically interact with the AF-2 transactivation domain of LRH-1 both in vivo and in

243 ocusing on the C-terminal ligand-binding and AF-2 transactivation domains, an assembly of an active t

244 ivators, their interaction also requires the AF-2 transactivation motif of VDR.

245 In contrast, the AF-2 transactivator is complex, spanning the 128-366 reg

246 on the presence of the conserved C-terminal AF-2 transcriptional activation motif.

247 elix 12 (AF2ER) minimized estrogen-dependent AF-2 transcriptional activation.

248 PRMT2 enhanced both ERalpha AF-1 and AF-2 transcriptional activity, and the potential methylt

249 FP) chimeras with full-length VDR (VDR-GFP), AF-2-truncated VDR (AF-2del-VDR-GFP), and ligand-binding

250 on activity of physically separated AF-1 and AF-2 using a novel hybrid reporter assay.

251 ) of RARgamma but not the C-terminal domain (AF-2) was required for association with beta-catenin, wh

252 n transcriptional synergism between AF-1 and AF-2, we expressed the amino terminal (AF-1-containing)

253 ion with beta-catenin, whereas both AF-1 and AF-2 were necessary for inhibition of beta-catenin trans

254 at the N terminus (AF-1) and the C terminus (AF-2) which work synergistically to confer full HNF-4 ac

255 transcription activation functions AF-1 and AF-2, which act in a promoter- and cell-specific manner.

256 transactivation domains, designated AF-1 and AF-2, which activate transcription in a cell type-indepe

257 -mediated activity from the separated mutant AF-2, which differed from the intact protein.

258 l activation domains, tau1 (AF-1), tau2, and AF-2, which were initially defined using transiently tra

259 istinct activation functions (AFs), AF-1 and AF-2, whose respective involvement varies in a cell type

260 f an estrogen-dependent activation function (AF-2) with p160 coactivators.

261 oxy-terminal transactivation function termed AF-2 within the last 15 amino acids of the ligand bindin