ライフサイエンスコーパス: SRC-3

1 s a direct target of protooncogene ACTR/AIB1/SRC-3.

2 , indicating that they are direct targets of SRC-3.

3 r turnover, and depletion of Pin1 stabilized SRC-3.

4 s, interacts selectively with phosphorylated SRC-3.

5 ain at 120 min, suggesting an oscillation of SRC-3.

6 urther reduced in TRbetaPV mice deficient in SRC-3.

7 utput, with a stronger similarity to AR than SRC-3.

8 te comparable expression levels of SRC-1 and SRC-3.

9 is important to identify genes regulated by SRC-3.

10 uding the androgen receptor (AR) coactivator SRC-3.

11 gron and promotes SPOP-dependent turnover of SRC-3.

12 dentified SI-2 as a highly promising SMI for SRC-3.

13 activity of the transcriptional coactivator SRC-3.

14 R (also named AIB1, RAC3, p/CIP, TRAM-1, and SRC-3), a member of the p160 family of coactivators for

15 egulation of steroid receptor coactivator-3 (SRC-3), a potent ERalpha coactivator.

16 ion of the nuclear receptor coactivator AIB1/SRC-3 acting in conjunction with estrogen receptor-alpha

17 In addition, Pin1 and SRC-3 activate nuclear-receptor-regulated transcription

18 transition from multi-(mono)ubiquitination (SRC-3 activation) to long-chain polyubiquitination (SRC-

19 rticipants in the phosphocode that regulates SRC-3 activity.

20 ough the amplified-in-breast cancer 1 (AIB1; SRC-3, ACTR, or NCoA3) was defined as a coactivator for

21 At the molecular level, SRC-3 acts synergistically with the transcription factor

22 SRC-1 (NCOA1), SRC-2 (TIF2/GRIP1/NCOA2), and SRC-3 (AIB1/ACTR/NCOA3).

23 The steroid receptor coactivator 3 gene (SRC-3) (AIB1/ACTR/pCIP/RAC3/TRAM1) is a p160 family tran

24 Steroid receptor coactivator-3 (SRC-3)/AIB1 is a member of the p160 nuclear receptor coa

25 In addition, SRC-3/AIB1 directly regulates transcription of matrix me

26 Here, we reported that the elevated SRC-3/AIB1 expression is significantly correlated with h

27 SRC-3/AIB1 is a master growth coactivator and oncogene,

28 SRC-3/AIB1 is a steroid receptor coactivator with potent

29 SRC-3/AIB1 is an important growth coactivator whose acti

30 Furthermore, SRC-3/AIB1 is associated with increased prostate cancer

31 SRC-3/AIB1 is required for focal adhesion turnover and f

32 We previously showed that SRC-3/AIB1 is required for prostate cancer cell prolifer

33 Taken together, these data suggest that SRC-3/AIB1 plays an essential role in prostate cancer ce

34 Steroid receptor coactivator 3 (SRC-3/AIB1) interacts with steroid receptors in a ligand

35 Steroid receptor coactivator-3 (SRC-3/AIB1) is a coactivator for nuclear receptors and o

36 Steroid receptor coactivator-3 (SRC-3/AIB1) is an oncogene frequently amplified and over

37 Steroid receptor co-activator-3 (SRC-3/AIB1) is an oncogene that is amplified and overexp

38 Steroid receptor coactivator 3 (SRC-3/AIB1/ACTR/NCoA-3) is a transcriptional coactivator

39 SRC-3/AIB1/ACTR/pCIP/RAC3/TRAM-1 is a primary transcript

40 evidence have indicated that the activity of SRC-3/AIB1/ACTR/pCIP/RAC3/TRAM1 could be regulated by ph

41 SRC-3/AIB1/ACTR/pCIP/RAC3/TRAM1 is a primary transcripti

42 SRC-1, SRC-2, and SRC-3 all enhanced IkappaB alpha transcription.

43 [nuclear receptor coactivator (NCOA)2], and SRC-3 [amplified in breast cancer 1 (AIB1)/NCOA3] are ke

44 osphorylated steroid receptor coactivator 3 (SRC-3), an oncogenic protein overexpressed in multiple h

45 ied as a direct target of oncogene AIB1/ACTR/SRC-3 and a transcriptional coregulator for estrogen and

46 aken together, our results clearly show that SRC-3 and AP-1 can coordinately regulate the transcripti

47 laps greatly with the gene signature of both SRC-3 and AR transcriptional output, with a stronger sim

48 ese two sites are located within a degron of SRC-3 and are primary determinants of SRC-3 turnover.

49 nce that Pin1 modulates interactions between SRC-3 and CBP/p300.

50 is dependent on a direct interaction between SRC-3 and ERalpha and can occur outside of the nucleus.

51 re used to determine the correlation between SRC-3 and ERalpha binding and recruitment of the transcr

52 duces (i) ligand-dependent colocalization of SRC-3 and ERalpha, (ii) the formation of ER-SRC-3 comple

53 ver, a mechanistic relationship between AIB1/SRC-3 and HER2/neu in the development of breast cancer h

54 PDXP and PP2A dephosphorylate SRC-3 and inhibit its ligand-dependent association with

55 CARM1 recruitment lags behind the binding of SRC-3 and p300 to ER.

56 omain protein (SPOP) interacts directly with SRC-3 and promotes its cullin 3-dependent ubiquitination

57 cancer cell invasiveness by phosphorylating SRC-3 and regulating SRC-3 proinvasive activity by site-

58 We also show that inhibition of SRC-3 and SRC-1 with SI-2, a second-generation SRC-3/SRC

59 lin as a potent small-molecule inhibitor for SRC-3 and SRC-1.

60 pears due to a decreased interaction between SRC-3 and the C8 subunit of the 20S core proteasome, thu

61 In breast cancer, high levels of AIB1/SRC-3 and the growth factor receptor HER2/neu predict re

62 nes in breast cancers and further found that SRC-3 and TRAF4 overexpression diminished cytotoxic stre

63 ected the underlying molecular mechanism for SRC-3 and TRAF4-mediated resistance to cytotoxic agents.

64 Patients with high SRC-3 and undetectable PTEN exhibited decreased recurren

65 Furthermore, AIB1/SRC-3(+/-) and (-/-) mice showed similarly delayed heali

66 In AIB1/SRC-3(+/-) and (-/-) mice, the angiogenic responses to s

67 cruitment of coactivators (SRC-1, SRC-2, and SRC-3) and corepressors (HDAC1, HDAC2, HDAC3, SMRT, and

68 lpha to recruit pCIP (AIB1/ACTR/RAC-3/TRAM-1/SRC-3) and p300 to a RARE did correlate with RA-associat

69 quires steroid receptor coactivators (SRC-2, SRC-3) and the mediator component MED14.

70 and steroid receptor coactivators SRC-2 and SRC-3, and changes in histone acetylation.

71 ed IKKalpha phosphorylation of ERalpha, AIB1/SRC-3, and histone H3.

72 to quantify links between PPARgamma, SRC-2, SRC-3, and lipogenesis.

73 ls through direct physical interactions with SRC-3, and selectively induce breast cancer cell death w

74 proteolysis assays using purified REGgamma, SRC-3, and the 20S proteasome reinforce these conclusion

75 n the G1 and S phases, recruitment of SRC-1, SRC-3, and, consequently, CBP is reduced in G1 phase des

76 Moreover, SRC-3(-/-) animals showed reduced body weight and adipos

77 nations of site-specific phosphorylations of SRC-3 are required for induction of IL-6 gene expression

78 our studies reveal an essential function of SRC-3 as a coordinator of inflammatory mRNA translation

79 ations in PC, and highlight the potential of SRC-3 as a therapeutic target in PC.

80 ta mRNAs in SRC-3(-/-) macrophages implicate SRC-3 as a translational repressor.

81 ively, these data suggest a crucial role for SRC-3 as an integrator of the complex transcriptional ne

82 e regulated tyrosine phosphorylation of AIB1/SRC-3 at a C-terminal tyrosine residue (Y1357) that is p

83 tyrosine kinase directly phosphorylates AIB1/SRC-3 at Y1357 and modulates the association of AIB1 wit

84 Here we report that deletion of the SRC-3 basic helix-loop-helix (bHLH) domain blocks its pr

85 identified two residues (K17 and R18) in the SRC-3 bHLH domain that are essential for its stability.

86 alyses of immunoprecipitated DNA to identify SRC-3-binding target genes in estradiol (E2)-treated MCF

87 ls individually depleted of SRC-1, SRC-2, or SRC-3 by small interfering RNA.

88 radation of the steroid receptor coactivator SRC-3 by the 20S proteasome in an ATP- and ubiquitin-ind

89 radation of the steroid receptor coactivator SRC-3 by the 20S proteasome in an ATP- and ubiquitin-ind

90 r amounts of cytokine mRNAs, suggesting that SRC-3 can exert effects at translational levels.

91 hat methylation promotes dissociation of the SRC-3/CARM1 coactivator complex.

92 d not significantly alter the mRNAs encoding SRC-3, CBP and the corepressors, NCoR and SMRT; or proge

93 by vitamin D, through VDR, was diminished in SRC-3(-/-) cells, suggesting an important role of SRC-3

94 Pin1 overexpression enhanced SRC-3 cellular turnover, and depletion of Pin1 stabilize

95 r epithelia and is required to modulate AIB1/SRC-3 coactivation of estrogen receptor alpha (ERalpha),

96 orylation-dependent ubiquitination regulates SRC-3 coactivator activation and transcriptional specifi

97 ts indicate that phosphorylation coordinates SRC-3 coactivator function by linking the probabilistic

98 activator of nuclear receptors by modulating SRC-3 coactivator protein-protein complex formation and

99 demonstrate that SMRT, like ERalpha and the SRC-3 coactivator, is recruited to an estrogen-responsiv

100 Steroid receptor coactivator 3 (SRC-3) coactivator phosphorylation has been shown to reg

101 show that PAX2 and the ER co-activator AIB-1/SRC-3 compete for binding and regulation of ERBB2 transc

102 SRC-3 and ERalpha, (ii) the formation of ER-SRC-3 complexes in cell lysates, and (iii) SRC-3 targeti

103 Together, we demonstrate that SRC-2 and SRC-3 concomitantly promote human adipocyte differentiat

104 Taken together, SRC-3 could play important roles through regulating mult

105 However, SRC-3 deficiency affected neither GH nor ALS expression.

106 f multiple signaling pathways indicated that SRC-3 deficiency could lead to (1) inhibition of cell cy

107 ctivation) to long-chain polyubiquitination (SRC-3 degradation) is processive during the transcriptio

108 of the 20S core proteasome, thus preventing SRC-3 degradation.

109 SRC-3 deletion impaired cellular proliferation and reduc

110 AIB1/SRC-3-dependent transcription and phenotypic changes, su

111 Herein, we show that AIB1/SRC-3 depletion from cultured endothelial cells reduces

112 ATP and AcCoA, as manifested by CBP/p300 and SRC-3 dismissal and SAGA and TFIID stabilization/recruit

113 y rescue screening approach, we identified a SRC-3 downstream gene-TRAF4 (tumor necrosis factor [TNF]

114 Together, our results show that SRC-3 drives CRPC formation and offer preclinical proof

115 In TRbetaPV mice deficient in SRC-3, dysfunction of the pituitary-thyroid axis and hyp

116 treated cells, lead to the identification of SRC-3/ERalpha-associated genes.

117 Both E2-dependent and -independent SRC-3/ERalpha-binding sites were identified.

118 AKT signaling is down-regulated in normally SRC-3-expressing tissues.

119 ent data, we have observed that reduction of SRC-3 expression by small interfering RNA decreases prol

120 AF4 expression is positively correlated with SRC-3 expression in human breast cancers.

121 Finally, we found that SRC-3 expression is inversely correlated with gefitinib

122 We observed that SRC-3 expression is inversely correlated with the expres

123 Furthermore, with decreased SRC-3 expression, proliferating cell nuclear antigen and

124 uggesting that ERalpha must directly contact SRC-3 for this posttranslational modification to take pl

125 tion is a potential regulatory mechanism for SRC-3 function, but the identity of such phosphatases re

126 eprogramming steroid receptor coactivator-3 (SRC-3) function by changing its posttranslational modifi

127 Twenty-seven percent of NSCLCs exhibited SRC-3 gene amplification, and we found that lung cancer

128 We identified 18 SRC-3 genomic binding sites and demonstrated estrogen re

129 y reveals that, in addition to degrading the SRC-3 growth coactivator, REGgamma also has a role in th

130 ted that the steroid receptor coactivator-3 (SRC-3) has a novel cytoplasmic function: it activates th

131 activator amplified in breast cancer 1 (AIB1/SRC-3) has a well-defined role in steroid and growth fac

132 Although multiple physiological roles of SRC-3 have been revealed, its involvement in the inflamm

133 cer 1 (AIB1)/steroid receptor coactivator-3 (SRC-3) have been shown to have a critical role in oncoge

134 ventual transcription-coupled degradation of SRC-3 in a phosphorylation- and Fbw7alpha dosage-depende

135 C phosphorylates and specifically stabilizes SRC-3 in a selective ER-dependent manner.

136 te that REGgamma promotes the degradation of SRC-3 in a ubiquitin- and ATP-independent manner.

137 cell proliferation and invasion functions of SRC-3 in breast cancer cells.

138 However, the role of SRC-3 in cancer cell proliferation and survival is still

139 activities and the protein concentrations of SRC-3 in cells through direct physical interactions with

140 l interfering RNA-mediated downregulation of SRC-3 in high-expressing, but not in low-expressing, lun

141 We documented elevated SRC-3 in human CRPC and in PTEN-negative human prostate

142 Homozygous deletion of SRC-3 in mice completely prevents Neu-induced tumor form

143 In contrast, knockdown of SRC-3 in PC3 (androgen receptor negative) prostate cance

144 ve to noncastrated counterparts, deletion of SRC-3 in Pten3CKO mice reversed all these changes.

145 In agreement with the role of SRC-3 in VDR function, the expression of several VDR tar

146 (-/-) cells, suggesting an important role of SRC-3 in VDR-mediated transactivation of the IGFBP-3 gen

147 role of the steroid receptor coactivator-3 (SRC-3) in thyroid carcinogenesis in vivo by using the of

148 its SRC-3-mediated effects, SPOP also exerts SRC-3-independent effects that are AR-mediated.

149 cer 1 (AIB1)/steroid receptor coactivator-3 (SRC-3) induces mammary tumorigenesis in mice.

150 Importantly, knockdown of ERK3 or SRC-3 inhibited the ability of lung cancer cells to inva

151 The related coactivators SRC-2 and SRC-3 interact with peroxisome proliferator activated re

152 Here we report that SRC-3 interacts with REGgamma, a proteasome activator kn

153 We propose that ubiquitination of SRC-3 is a phospho-mediated biphasic event and that a tr

154 strate that an acidic residue-rich region in SRC-3 is an important determinant for aPKC-mediated phos

155 Taken together, these findings indicate that SRC-3 is an important regulator of prostate cancer proli

156 ported that the transactivation potential of SRC-3 is controlled in part by PTMs, although this data

157 SRC-3 is frequently amplified and/or overexpressed in ho

158 SRC-3 is frequently amplified or overexpressed in a numb

159 Although SRC-3 is highly expressed in advanced prostate cancer, i

160 In this study, we show that SRC-3 is overexpressed in prostate cancer patients and i

161 Methylation of SRC-3 is regulated by estrogen signaling in MCF7 cells a

162 Our data indicate that AIB1/SRC-3 is required for HER2/neu oncogenic activity and fo

163 Previous studies indicate that SRC-3 is required for normal animal growth and is often

164 studies indicate that the cellular level of SRC-3 is tightly regulated by both ubiquitin-dependent a

165 its function in stromal cells, although AIB1/SRC-3 is up-regulated in tumor stroma and may, thus, con

166 he oncogenic steroid receptor coactivator-3 (SRC-3) is a critical regulator of white adipocyte develo

167 Steroid receptor coactivator-3 (SRC-3) is a histone acetyltransferase and nuclear hormon

168 Steroid receptor coactivator-3 (SRC-3) is a transcriptional coactivator for nuclear rece

169 Steroid receptor coactivator 3 (SRC-3) is an oncogenic nuclear receptor coactivator that

170 The steroid receptor coactivator 3 (SRC-3) is overexpressed in a wide range of cancers, driv

171 ivity of the Steroid Receptor Coactivator-3 (SRC-3) is reduced upon HER2 inhibition, and recruitment

172 Kalpha, in conjunction with ERalpha and AIB1/SRC-3, is important in activating the transcription of e

173 SRC-2 and SRC-3 knockdown increases the proportion of cells in a P

174 rrelated with gefitinib sensitivity and that SRC-3 knockdown results in epidermal growth factor recep

175 a potent signaling mechanism for regulating SRC-3 levels in cells by coordinate enzymatic inhibition

176 We predict that reducing AIB1/SRC-3 levels or activity in the mammary epithelium could

177 Here, we exploited the mifepristone-induced SRC-3 LNCaP prostate cancer cell line generated in our l

178 EK1/2) pathway induce a cytoplasmic shift in SRC-3 localization, whereas stimulation by epidermal gro

179 e-associated TNF-alpha and IL-1beta mRNAs in SRC-3(-/-) macrophages implicate SRC-3 as a translationa

180 In response to LPS, SRC-3(-/-) macrophages produce significantly more proinf

181 Therefore, SRC-3 maintains IGF-I in the circulation through enhanci

182 Taken together, these data suggest that SRC-3 may be an important oncogene and therapeutic targe

183 SRC-3 may cooperate with other translational repressors

184 his finding suggests that in addition to its SRC-3-mediated effects, SPOP also exerts SRC-3-independe

185 However, the mechanisms of SRC-3-mediated growth regulation remain unclear.

186 hat restoration of SPOP expression inhibited SRC-3-mediated oncogenic signaling and tumorigenesis, th

187 TRbeta(PV/PV) mice with SRC-3 (TRbeta(PV/PV)SRC-3(+/+) mice).

188 By ages 3 to 4 months, Neu/SRC-3(+/-) mice exhibit a noticeable reduction in latera

189 Herein we show that SRC-3(-/-) mice are markedly hypersensitive to LPS-induc

190 The low IGF-I level in SRC-3(-/-) mice was not due to the failure of IGF-I mRNA

191 ause IGF-I and IGFBP-3 stabilize each other, SRC-3(-/-) mice were crossbred with the liver-specific t

192 rculating IGF-I was significantly reduced in SRC-3(-/-) mice with the C57BL/6J background.

193 PV/PV) mice deficient in SRC-3 (TRbeta(PV/PV)SRC-3(-/-) mice) had significantly increased survival, d

194 vel was significantly increased over that in SRC-3(-/-) mice, but the IGFBP-3 level failed to increas

195 several VDR target genes was also reduced in SRC-3(-/-) mice.

196 nsible factor that limits the IGF-I level in SRC-3(-/-) mice.

197 Furthermore, IGFBP-3 mRNA was reduced in SRC-3(-/-) mice.

198 ffspring from the cross of TRbeta(PV/PV) and SRC-3(-/-) mice.

199 Thus, SRC-3 modulates RTH by at least two mechanisms, one via

200 We conclude that AIB1/SRC-3 modulates stromal cell responses via cross-talk wi

201 through limiting concentrations of the same SRC-3 molecule to exert different physiological function

202 Indeed, in SRC-3(-/-) mouse embryonic fibroblasts, adipocyte differ

203 0 T antigen NLS to the cytoplasmic localized SRC-3 mutant drives it back into the nucleus and restore

204 lasmic localization of a nonphosphorylatable SRC-3 mutant further supported these results.

205 interaction between VDR and the coactivator, SRC-3 (NCOA3), thereby increasing transcriptional activi

206 und ERalpha, steroid receptor coactivator 3 (SRC-3/NCOA3), and a secondary coactivator (p300/EP300).

207 SRC-3 NLS mutants block its translocation into the nucle

208 Similarly, in prostate glands of SRC-3 null mice, expressions of these components in the

209 Similarly, in SRC-3 null mutant mice, AKT signaling is down-regulated

210 dicate that proteasome-dependent turnover of SRC-3 occurs in the nucleus and that two amino acid resi

211 the steroid hormone receptor coactivator 3 (SRC-3) on RTH.

212 ntify SRC-3Delta4, a splicing isoform of the SRC-3 oncogene, as a signaling adaptor that links EGFR a

213 olecular mechanisms that regulate 'activated SRC-3 oncoprotein' turnover during tumorigenesis remain

214 also promoting the turnover of the activated SRC-3 oncoprotein.

215 ify SMIs for steroid receptor coactivator-3 (SRC-3 or AIB1), a large and mostly unstructured nuclear

216 ogate p53 function, our results suggest that SRC-3 overexpression may be especially important in tumo

217 Similar to that observed for SRC-3 overexpression, breast cancer cells overexpressing

218 Steroid receptor coactivator-3 (SRC-3, p/CIP, AIB1, ACTR, RAC3, and TRAM-1) is a member

219 organization of the pre-existing ERE/ERalpha/SRC-3/p300 complex.

220 ot bind T3, could not interact directly with SRC-3/PA28gamma to activate proteasome degradation, resu

221 SPOP interacts directly with an SRC-3 phospho-degron in a phosphorylation-dependent mann

222 In Neu-induced tumors, high levels of SRC-3, phosphorylated Neu, cyclin D1, cyclin E, and prol

223 l regulation whereby specific modulations of SRC-3 phosphorylation allow this coactivator to function

224 echanisms involved in estradiol (E2)-induced SRC-3 phosphorylation and found that this occurs only wh

225 ether these data demonstrate that E2-induced SRC-3 phosphorylation is dependent on a direct interacti

226 Six SRC-3 phosphorylation sites have been identified, and th

227 ful identification of six functional in vivo SRC-3 phosphorylation sites.

228 ligand binding domain inhibit E2-stimulated SRC-3 phosphorylation, as do mutations in the nuclear re

229 calizes to the cytoplasm supports E2-induced SRC-3 phosphorylation.

230 domain did not block this rapid E2-dependent SRC-3 phosphorylation.

231 The transcriptional coactivator SRC-3 plays a key role in enhancing prostate cancer cell

232 ER) recruits steroid receptor coactivator-3 (SRC-3) primary coactivator and secondary coactivators, p

233 ness by phosphorylating SRC-3 and regulating SRC-3 proinvasive activity by site-specific phosphorylat

234 convincing evidence that these mutations in SRC-3 promoted enhanced transcription of the IGFBP3 gene

235 role in PC cells, promoting the turnover of SRC-3 protein and suppressing androgen receptor transcri

236 PP1 stabilizes SRC-3 protein by blocking its proteasome-dependent turno

237 Bufalin strongly promoted SRC-3 protein degradation and was able to block cancer c

238 n experiments suggest that REGgamma promotes SRC-3 protein degradation.

239 e 19S proteasome regulatory cap, targets the SRC-3 protein for degradation.

240 ntly inhibit primary tumor growth and reduce SRC-3 protein levels in a breast cancer mouse model.

241 associated SPOP mutants cannot interact with SRC-3 protein or promote its ubiquitination and degradat

242 ERalpha monomers independently recruits one SRC-3 protein via the transactivation domain of ERalpha;

243 of its ability to promote degradation of the SRC-3 protein.

244 receptor, which supports a role for AF-1 in SRC-3 recruitment.

245 line generated in our laboratory to identify SRC-3-regulated genes by oligonucleotide microarray anal

246 ctors and hormones induce phosphorylation of SRC-3, regulating its function and contributing to its o

247 its importance, the functional regulation of SRC-3 remains poorly understood within a cellular contex

248 oid receptor coactivators (SRC-1, SRC-2, and SRC-3) represent emerging targets in cancer therapeutics

249 Because of SRC-3's ability to abrogate p53 function, our results su

250 ning of human Ser/Thr phosphatases targeting SRC-3's known phosphorylation sites, the phosphatases PD

251 SRC-3 shows a time-dependent decay in the presence of cy

252 SRC-3 signal was increased at 30 min, reduced at 60 min,

253 Here, we show that deletion of one allele of SRC-3 significantly delays Neu-induced mammary tumor dev

254 As a SRC-3 SMI, SI-2 can selectively reduce the transcription

255 dominant, pro-adipogenic roles for SRC-2 and SRC-3, SRC-1 knockdown does not affect adipogenesis.

256 C-3 and SRC-1 with SI-2, a second-generation SRC-3/SRC-1 small-molecule inhibitor, targets the CSC/TI

257 oid receptor coactivators (SRC-1, SRC-2, and SRC-3) steer the functional output of numerous genetic p

258 We reported previously that SRC-3 stimulated prostate cell growth in a hormone-indep

259 n this study, we show that overexpression of SRC-3 stimulates cell growth to increase cell size in pr

260 Without any SRC-3 structural information, we identified SI-2 as a hi

261 n the nuclear receptor-interacting domain of SRC-3, suggesting that ERalpha must directly contact SRC

262 Here we report that SRC-3 supports the TIC/CSC state and induces an epitheli

263 R-SRC-3 complexes in cell lysates, and (iii) SRC-3 targeting to a visible, ERalpha-occupied and -regu

264 C), which in turn expressed higher levels of SRC-3 than did cultured primary human HBECs.

265 cancer cell lines expressed higher levels of SRC-3 than did immortalized human bronchial epithelial c

266 overed a critical "actron/degron" element in SRC-3 that is required for this phosphorylation-dependen

267 ence for an early nongenomic action of ER on SRC-3 that supports the well-established downstream geno

268 he nuclear hormone receptor coactivator AIB1/SRC-3, the question of whether either IKKalpha or IKKbet

269 ghput, and fluorescent microscopy, we report SRC-3 to be a nucleocytoplasmic shuttling protein whose

270 We found SRC-3 to be overexpressed in 27% of non-small cell lung

271 e association of IKKalpha, ERalpha, and AIB1/SRC-3 to estrogen-responsive promoters and increased IKK

272 ced upon HER2 inhibition, and recruitment of SRC-3 to regulatory elements of endogenous genes is impa

273 Interestingly, we showed that recruitment of SRC-3 to two target promoters, IRS-2 and IGF-I, requires

274 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an AR-ROR response element (RORE) to stimulate

275 ent degradation as well as for regulation of SRC-3 transcriptional coactivator capacity.

276 as a molecular switch for disassembly of the SRC-3 transcriptional coactivator complex.

277 identified to be key negative regulators of SRC-3 transcriptional coregulatory activity in steroid r

278 sis as compared with TRbeta(PV/PV) mice with SRC-3 (TRbeta(PV/PV)SRC-3(+/+) mice).

279 TRbeta(PV/PV) mice deficient in SRC-3 (TRbeta(PV/PV)SRC-3(-/-) mice) had significantly i

280 In SRC-3(-/-)/TTR-IGF-I mice, the IGF-I level was significa

281 cyclin E are significantly decreased in Neu/SRC-3(+/-) tumors, proliferation is reduced, and AKT and

282 ron of SRC-3 and are primary determinants of SRC-3 turnover.

283 /CUL3/Rbx1 ubiquitin ligase complex promotes SRC-3 turnover.

284 )-based ubiquitin ligase, is responsible for SRC-3 ubiquitination and proteolysis.

285 vered a nonproteolytic "activation" code for SRC-3 ubiquitination induced by Fbw7alpha.

286 We found that SRC-3 up-regulates the expression of multiple genes in t

287 n was severely impaired, and reexpression of SRC-3 was able to restore it.

288 atin immunoprecipitation assay revealed that SRC-3 was directly recruited to the promoters of these g

289 Methylation of SRC-3 was localized to an arginine in its CARM1 binding

290 ACTR (also called AIB1 and SRC-3) was identified as a coactivator for nuclear recep

291 st the physiological implications of PTMs on SRC-3, we developed a knock-in mouse model containing mu

292 and lipogenesis, without changes in SRC-2 or SRC-3, we hypothesized that permissive coregulator level

293 ns, we generated mice in which both Pten and SRC-3 were inactivated in prostate epithelial cells (Pte

294 TRbeta with steroid receptor coactivator 3 (SRC-3), which recruits proteasome activator PA28gamma.

295 ompanied by an increase in nuclear levels of SRC-3, which accumulates to high levels specifically in

296 his equilibrium by down-regulating SRC-2 and SRC-3 while simultaneously quantifying PPARgamma.

297 nteractions of differentially phosphorylated SRC-3 with downstream transcriptional activators and coa

298 Finally, knockdown of SRC-3 with inducible short hairpin RNA expression in pro

299 ion at S857 was essential for interaction of SRC-3 with the ETS transcription factor PEA3, which prom

300 vels of phosphorylated Neu compared with Neu/SRC-3(wt) mice.