ライフサイエンスコーパス: beta-TrCP

1 beta-TrCP and SKP2 are two well-studied F-box proteins,

2 beta-TrCP binds to IkappaBalpha only when the latter is

3 beta-TrCP F-box protein mediates ubiquitination of phosp

4 beta-TrCP function is essential for the induction of nuc

5 beta-TrCP thus plays a critical role in both canonical a

6 beta-TrCP ubiquitinates EZH2 and Jak2-mediated phosphory

7 beta-TrCP ubiquitinates LPCAT1 at an acceptor site (Lys(

8 beta-TrCP, the substrate recognition subunit of SCF-type

9 SCF complex, a heterotetramer (Skp1, Cul-1, beta-TrCP [F-box protein], and ROC1) involved with ubiqu

10 e presence of HPV-16 E7, including cullin 1, beta-TrCP, Aurora A, and Polo-like kinase-1 (PLK1).

11 A beta-TrCP mutant lacking the F-box inhibits the signal-i

12 augmentation was also inhibited by Vpu in a beta-TrCP-dependent manner.

13 entified PHLPP1 as a proteolytic target of a beta-TrCP-containing Skp-Cullin 1-F-box protein (SCF) co

14 We focused on SNAT1, a beta-TrCP-dependent Vpu substrate.

15 f beta-TrCP reduced the expression of Sp1, a beta-TrCP substrate, which, in turn, reduced Skp2 gene e

16 CG12 to mimic glucose starvation to activate beta-TrCP-mediated Sp1 degradation has translational pot

17 ay is Siah2 and APC dependent, but GSK-3 and beta-TrCP independent.

18 howed increased cytosolic levels of Axin and beta-TrCP and decreased phosphorylation of glycogen synt

19 wn to act as a scaffold for beta-catenin and beta-TrCP and thereby to potentiate beta-TrCP-mediated b

20 Endogenous beta-catenin and beta-TrCP could be coimmunoprecipitated from mammalian c

21 odulating the expression of beta-catenin and beta-TrCP, suggesting the translation potential of using

22 correlated during cell cycle with FBXW2 and beta-TrCP/SKP2 being high or low, respectively, in arres

23 ated PD-L1 forms a complex with GSK3beta and beta-TrCP.

24 SP1 proteins to target IRF3, IRF5, IRF7, and beta-TrCP for degradation.

25 nately regulated by Pak1 phosphorylation and beta-TrCP-dependent ubiquitin-proteasome pathways.

26 IkappaB kinase-dependent phosphorylation and beta-TrCP-dependent ubiquitylation of the N-terminal sig

27 first time that interaction between PRLr and beta-TrCP is less efficient in human breast cancer cells

28 Moreover, we determined that Skp2 and beta-TrCP are mutually regulated, providing a feedback m

29 hysical association of Cdc25A with Smad3 and beta-TrCP.

30 n of Mcl-1 with the E3 ligase beta-TrCP, and beta-TrCP then facilitates the ubiquitination and degrad

31 d to be required for maximal binding between beta-TrCP and phosphorylated I kappaB alpha.

32 ncogenic REST-FS mutant, which does not bind beta-TrCP.

33 stable REST mutant, which is unable to bind beta-TrCP, inhibited Mad2 expression and resulted in a p

34 -TrCP degron sequence that was found to bind beta-TrCP.

35 in lymphoma pathogenesis are unable to bind beta-TrCP.

36 nsistent with their proposed role in binding beta-TrCP.

37 Microtubule inhibition blocked beta-TrCP-mediated proteasomal processing of Gli2 in ost

38 E1A in virus-transformed cells reduced both beta-TrCP and ubiquitination of nuclear REST.

39 sults indicate that the turnover of Mcl-1 by beta-TrCP is an essential mechanism for GSK-3beta-induce

40 s ubiquitination dependent and controlled by beta-TrCP.

41 dependent proteasome degradation of PD-L1 by beta-TrCP.

42 t of the phosphorylation sites recognized by beta-TrCP.

43 G motif whose phosphorylation is targeted by beta-TrCP E3 ligase during interphase.

44 yses indicate that cyclin D1 was targeted by beta-TrCP through an unconventional recognition site, (2

45 first evidence that cyclin D1 is targeted by beta-TrCP.

46 eventing proteasomal degradation of Twist by beta-TrCP.

47 SK-3beta and then cannot be ubiquitinated by beta-TrCP, is much more stable than wild-type Mcl-1 and

48 ppaB to the nucleus by sequestering cellular beta-TrCP, a protein required for the degradation of the

49 required Vpu's ability to bind the cellular beta-TrCP-E3-ubiquitin ligase complex.

50 DMRT1 contains a consensus beta-TrCP degron sequence that was found to bind beta-Tr

51 We found two conserved beta-TrCP recognition motif (DSGVVYS and DSGSIVVS) in th

52 to target the latter for degradation by CRL1(beta-TrCP) and so inhibit origin firing.

53 Two ubiquitin ligases, the Skp1-cullin-beta-TrCP (SCFbeta-TrCP) complex and the anaphase-promot

54 Stabilized ATF4 mutants exhibit decreased beta-TrCP degron phosphorylation, beta-TrCP interaction,

55 ion of either binding site in Nrf2 decreased beta-TrCP-mediated ubiquitylation of the transcription f

56 ak2-mediated phosphorylation on Y641 directs beta-TrCP-mediated EZH2 degradation.

57 8-facilitated beta-catenin ablation, ectopic beta-TrCP expression enhanced the degradation.

58 e Sp1 degradation, suppression of endogenous beta-TrCP function by a dominant-negative mutant or smal

59 n of PHLPP1, whereas knockdown of endogenous beta-TrCP has the opposite effect.

60 ull-down analysis with bacterially expressed beta-TrCP.

61 This facilitates beta-TrCP binding and ubiquitin-mediated proteolysis of

62 ylation within a canonical phosphodegron for beta-TrCP docking and site-specific ubiquitination.

63 her, our findings demonstrate a key role for beta-TrCP in controlling the level of PHLPP1, and activa

64 LPCAT1 is the first lipogenic substrate for beta-TrCP, and the results suggest that modulation of th

65 tion of Gsk3beta ubiquitination and Gsk3beta-beta-TrCP binding.

66 monoubiquitination of Gsk3beta and Gsk3beta-beta-TrCP interaction.

67 ased monoubiquitination of Gsk3beta/Gsk3beta-beta-TrCP association suppressed beta-catenin recruitmen

68 n accumulation requires Wnt-induced GSK3beta/beta-TrCP interaction; the current study revealed that p

69 ng axis composed of p38 MAP kinase-MK2-Hsp27-beta-TrCP may promote AUF1 degradation by proteasomes an

70 In this study, we have identified beta-TrCP as the ubiquitin ligase for lysosomal degradat

71 a specific recognition site for E3RS(IkappaB/beta-TrCP), an SCF-type E3 ubiquitin ligase, thereby exp

72 Moreover, immunopurified beta-TrCP ubiquitinates phosphorylated IkappaBalpha at s

73 novel SCF(beta-TrCP) substrate and implicate beta-TrCP as an important negative regulator of PRL sign

74 ation of cells, and deletion of the F-box in beta-TrCP abolishes its ability to ubiquitinate IkappaBb

75 Heterozygous deletion of Dmrt1 in beta-TrCP-deficient spermatogonia increased meiotic cell

76 s showed intracellular accumulation of FN in beta-TrCP siRNA-treated cells without showing much alter

77 tion dysfunction and alleviates mucositis in beta-TrCP-deficient mice.

78 cumulation of DMRT1 at the Stra8 promoter in beta-TrCP-deficient testes.

79 idative modification of cysteine residues in beta-TrCP.

80 dependent upon the WD40 repeat sequences in beta-TrCP and on phosphorylation of the GSK3beta sites i

81 It is noteworthy that this drug-induced beta-TrCP up-regulation was accompanied by the concomita

82 Smad3 siRNA inhibits beta-TrCP-Cdc25A interaction and Cdc25A degradation in r

83 and the concurrent down-regulation of known beta-TrCP substrates examined, including Wee1, Ikappabet

84 appears to inhibit binding of the E3 ligase beta-TrCP and prevents beta-catenin ubiquitination and d

85 the association of Mcl-1 with the E3 ligase beta-TrCP, and beta-TrCP then facilitates the ubiquitina

86 and substrate of the SCF E3 ubiquitin ligase beta-TrCP (FBXW1).

87 owing for binding of the E3-ubiquitin ligase beta-TrCP and consequently ubiquitylation.

88 ctive recruitment of the E3-ubiquitin ligase beta-TrCP to phospho-IkappaBalpha proteosomal degradatio

89 a Delta F-box mutant of the ubiquitin ligase beta-TrCP, which serves as a specific substrate trap for

90 that although small interfering RNA-mediated beta-TrCP knockdown protected cells against STG28-facili

91 ruction box ((727)DSGAGS(732)) that mediates beta-TrCP recognition and encompasses a glycogen synthas

92 Moreover, beta-TrCP expression was up-regulated in response to STG

93 ssion of wild-type but not DeltaF-box mutant beta-TrCP leads to decreased expression and increased ub

94 CP to a specific site, and dominant negative beta-TrCP blocks phosphorylation-dependent degradation o

95 by forced expression of a dominant-negative beta-TrCP mutant suppresses growth and survival of human

96 However, the action of Ras/NORE1A/beta-TrCP is substrate-specific because IkappaB, another

97 Specifically, cellular accumulation of beta-TrCP reduced the expression of Sp1, a beta-TrCP sub

98 K1 or IKKbeta) also leads to accumulation of beta-TrCP.

99 e C terminus of REST critical for binding of beta-TrCP and targeting of REST for proteasomal degradat

100 We found that the binding of beta-TrCP to beta-catenin was direct and dependent upon

101 quitin ligase activity as well as binding of beta-TrCP to phosphorylated I kappaB alpha was decreased

102 ggested that the NSP1-induced degradation of beta-TrCP is an uncommon mechanism of subverting IFN-bet

103 Depletion of beta-TrCP reduced FAF1-mediated beta-catenin polyubiquit

104 Depletion of beta-TrCP stabilized AUF1.

105 small interfering RNA-mediated knock-down of beta-TrCP enhanced and protected against STG28-facilitat

106 Although ectopic expression of beta-TrCP enhanced the ability of OSU-CG12 to facilitate

107 itutive processing of p100 is independent of beta-TrCP but rather is regulated by the nuclear shuttli

108 rocessing of p100 mutants was independent of beta-TrCP.

109 s not required for JNK-mediated induction of beta-TrCP.

110 In addition, inhibition of beta-TrCP augments the antiproliferative effects of anti

111 Here we show that inhibition of beta-TrCP either by RNAi approach or by forced expressio

112 The involvement of beta-TrCP in beta-catenin degradation was also corrobora

113 Knockdown of beta-TrCP expression inhibits the ubiquitination and deg

114 ce an increase in the steady state levels of beta-TrCP mRNA and protein levels in human cells.

115 The mechanisms of beta-TrCP induction via stress and its role in NF-kappaB

116 In contrast, overexpression of beta-TrCP enhanced ubiquitination and degradation of AUF

117 Overexpression of beta-TrCP induced the ubiquitylation and degradation of

118 ation suppressed beta-catenin recruitment of beta-TrCP, leading to long-term inhibition of beta-caten

119 cular determinant of GSK3beta recruitment of beta-TrCP.

120 motif of TRIM9 and the WD40 repeat region of beta-TrCP prevented beta-TrCP from binding its substrate

121 itor or by siRNA-mediated down-regulation of beta-TrCP.

122 We have examined the role of beta-TrCP (beta-transducin repeat-containing protein) in

123 To appreciate tissue-specific roles of beta-TrCP, we studied the consequences of inducible abla

124 RNA interference-mediated silencing of beta-TrCP or inhibition of Jak2 results in EZH2 stabiliz

125 ubstrates, Vpu leads to the stabilization of beta-TrCP substrates such as beta-catenin, IkappaBalpha,

126 (NF-kappa-B inhibitor), a known substrate of beta-TrCP, was rescued by Src, suggesting a wider effect

127 AUF1 is a target of beta-TrCP, the substrate recognition subunit of the E3 u

128 by Src, suggesting a wider effect of Src on beta-TrCP substrates.

129 -catenin is destabilized and is GSK-3beta or beta-TrCP independent.

130 decreased beta-TrCP degron phosphorylation, beta-TrCP interaction, and ubiquitination, as well as el

131 enin and beta-TrCP and thereby to potentiate beta-TrCP-mediated beta-catenin ubiquitination and degra

132 he WD40 repeat region of beta-TrCP prevented beta-TrCP from binding its substrates, stabilizing Ikapp

133 ecruits the ubiquitin ligase adapter protein beta-TrCP to a specific site, and dominant negative beta

134 nd by interacting with F-box-binding protein beta-TrCP, undergoes ubiquitin-dependent proteolysis.

135 nd Ser33 are recognized by the F-box protein beta-TrCP, a component of a ubiquitin ligase complex tha

136 t REST is an interactor of the F-box protein beta-TrCP.

137 lation and did not require the F box protein beta-TrCP.

138 ependent interactions with the F box protein beta-TrCP.

139 s beta-transducin repeat-containing protein (beta-TrCP) and mediates proteasomal degradation of CD4.

140 t beta-transducin repeat-containing protein (beta-TrCP) E3 ubiquitin ligase is required for Gli2 degr

141 f beta-transducin repeat-containing protein (beta-TrCP) expression represents a cellular response in

142 e beta-transducin repeat-containing protein (beta-TrCP) is required for FAF1 to suppress Wnt signalin

143 t beta-transducin repeat-containing protein (beta-TrCP) targets Sp1 for proteasomal degradation in re

144 beta-transducin repeats-containing protein (beta-TrCP) ubiquitin-protein isopeptide ligase.

145 f beta-transducin repeat-containing protein (beta-TrCP), a component of the SCF ubiquitin ligase comp

146 e beta-transducin repeat-containing protein (beta-TrCP), a component of the Skp-Cullin-F-box-containi

147 f beta-transducin repeat-containing protein (beta-TrCP), an F-box component of the Skp1-Cul1-F-box pr

148 , beta-transducin repeat-containing protein (beta-TrCP), and occurs only in the cytoplasm, the consti

149 , beta-transducin repeat-containing protein (beta-TrCP), that polyubiquitinates LPCAT1, thereby targe

150 r beta-transducin repeat-containing protein (beta-TrCP), which acts as a substrate receptor for the S

151 (beta-transducin repeat-containing protein [beta-TrCP]).

152 iates with the SCF (Skp1-Cul1-F-box protein)-beta-TrCP complex.

153 via a mechanism involving the F-box protein, beta-TrCP (SLIMB in Drosophila).

154 ex containing the F-box/WD40-repeat protein, beta-TrCP, a vertebrate homolog of Drosophila Slimb.

155 beta-Transducin repeat-containing proteins (beta-TrCP) serve as substrate recognition component of E

156 Beta-transducin repeats-containing proteins (beta-TrCP) serve as the substrate recognition subunits f

157 beta-transducin repeats-containing proteins (beta-TrCP)-mediated degradation due to phosphorylation b

158 ta (GSK-3beta) phosphorylation that recruits beta-TrCP docking within the enzyme.

159 liver triglyceride content, through reduced beta-TrCP-mediated degradation of the Akt phosphatase, P

160 n this regulatory pathway is to create a SCF(beta-TrCP) E3 ubiquitin ligase binding site for beta-cat

161 etween phosphorylated I kappaB alpha and SCF(beta-TrCP) but no change in the composition of the SCF(b

162 new gene (RING) E3 enzymes SCF(Cdc4) and SCF(beta-TrCP) work with the E2 Cdc34 to build polyubiquitin

163 e association between I kappaB alpha and SCF(beta-TrCP).

164 vidence that the distinct Cullin-1 based SCF(beta-TrCP)complex regulates beta-catenin stability, our

165 rylated PRLR undergoes ubiquitination by SCF(beta-TrCP) in vitro.

166 kp-Cullin 1-F-box protein (SCF) complex (SCF(beta-TrCP)) E3 ubiquitin ligase in a phosphorylation-dep

167 igase Skp1-cullin-F-box protein complex, SCF(beta-TrCP).

168 tination of I kappaB alpha and decreased SCF(beta-TrCP) ubiquitin ligase activity.

169 n and degradation of a target of the E3- SCF(beta-TrCP) ubiquitin ligase, the NF-kappaB inhibitor Ika

170 itination, a process catalyzed by the E3-SCF(beta-TrCP) ubiquitin ligase.

171 Lipopolysaccharide-induced SCF(beta-TrCP) ubiquitin ligase activity as well as binding

172 egraded by means of the ubiquitin ligase SCF(beta-TrCP) during the G2 phase of the cell cycle to allo

173 t are recognized by the ubiquitin ligase SCF(beta-TrCP), since deletion or mutation of either degron

174 cyclin D1 by up-regulating the E3 ligase SCF(beta-TrCP), we hypothesized that beta-transducin repeat-

175 ng their ubiquitination by the E3 ligase SCF(beta-TrCP).

176 These data indicate that PRLR is a novel SCF(beta-TrCP) substrate and implicate beta-TrCP as an impor

177 at allows for the specific regulation of SCF(beta-TrCP) targets.

178 imulate the ubiquitin ligase activity of SCF(beta-TrCP) toward its target beta-catenin, resulting in

179 ic because IkappaB, another substrate of SCF(beta-TrCP), is not sensitive to NORE1A-promoted degradat

180 hosphorylated IkappaB via recruitment of SCF(beta-TrCP)-Roc1 E3 ubiquitin ligase complex.

181 he Src tyrosine kinase as a regulator of SCF(beta-TrCP).

182 ed motifs present in other substrates of SCF(beta-TrCP).

183 r beta (TGF-beta)-Smad3 pathway promotes SCF(beta-TrCP)-mediated Cdc25A ubiquitination.

184 Here we show that the SCF(beta-TrCP) binding site created by phosphorylation of be

185 ild-type APC protein is recruited to the SCF(beta-TrCP) complex, ubiquitin conjugated, and degraded.

186 but no change in the composition of the SCF(beta-TrCP) complex.

187 s a substrate recognition subunit of the SCF(beta-TrCP) E3 ubiquitin ligase.

188 nstead, we found that Src attenuates the SCF(beta-TrCP) E3-ligase activity in blunting Taz proteasoma

189 at these residues by PP2A eliminates the SCF(beta-TrCP) recognition site and blocks beta-catenin ubiq

190 e substrate recognition component of the SCF(beta-TrCP) ubiquitin ligase complex.

191 Multiple components of the SCF(beta-TrCP)-based claspin degradation machinery were foun

192 volves deregulation of components of the SCF(beta-TrCP)-based claspin degradation machinery.

193 Thus, SCF(beta-TrCP)-dependent degradation of REST during G2 permi

194 Plk1 kinase activity and is mediated by SCF-beta-TrCP.

195 t interacts with the Plk1 kinase and the SCF-beta-TrCP ubiquitin ligase.

196 By sequestering beta-TrCP away from other cellular substrates, Vpu leads

197 This Skp2-beta-TrCP-Sp1 feedback loop represents a novel crosstalk

198 reasoned that the human homologs of Slimb - beta-TrCP and its isoform beta-TrCP2 (KIAA0696) - might

199 sphorylation of Ci and mediation of Ci-Slimb/beta-TrCP binding.

200 d for recognition by the F box protein SLIMB/beta-TrCP and proteasomal degradation.

201 ducin repeats-containing protein) (SCF(Slimb/beta-TrCP)) as the E3 ubiquitin ligase complex responsib

202 and genetic data strongly suggest that Slimb/beta-TrCP is the specificity determinant for the signal-

203 Targeting beta-TrCP to Cdc25A requires phosphorylation of serines

204 l cancer as well as prospective of targeting beta-TrCP as a means of anticancer therapy are also disc

205 rovide the proof of principle that targeting beta-TrCP might be beneficial for anticancer therapies.

206 Evidence indicates that Skp2 targets beta-TrCP for degradation via the cyclin-dependent kinas

207 We conclude that beta-TrCP is a component of an E3 ubiquitin ligase that

208 Our studies demonstrate that beta-TrCP has an important role in controlling H3K27 tri

209 We demonstrate that beta-TrCP interacts specifically with IkappaBbeta, and s

210 interference technique, we demonstrated that beta-TrCP is essential for NIK-induced p100 ubiquitinati

211 Therefore, these results indicate that beta-TrCP plays a critical role in the activation of NF-

212 Collectively, our data indicate that beta-TrCP regulates the transition from mitosis to meios

213 icantly, our pull-down assays indicated that beta-TrCP binds a phosphorylated version of DSGIS more t

214 vide an explanation for the observation that beta-TrCP can act as a tumor suppressor or an oncogene i

215 Here, we show that beta-TrCP, the substrate recognition component of an E3

216 These results suggest that beta-TrCP is an essential component of NIK-induced p100

217 The beta-TrCP-deficient male germ cells did not enter meiosi

218 ssociated with Cdc25A phosphorylation at the beta-TrCP docking site (DS82G motif) and physical associ

219 V3 was post transcriptional, mediated by the beta-TrCP ubiquitin E3 ligase and occurred via an endoly

220 ubsequent processing of p100 mediated by the beta-TrCP ubiquitin ligase and 26 S proteasome, respecti

221 Cysteine 308 in Blade 1 of the beta-TrCP beta-propeller region was found to be required

222 Transcription of the beta-TrCP gene is not required for JNK-mediated inductio

223 chanism for TRIM9-mediated regulation of the beta-TrCP SCF complex activity but also identifies TRIM9

224 Collectively, our data show that the beta-TrCP-FBXW2-SKP2 axis forms an oncogene-tumour suppr

225 In addition, we show that the beta-TrCP-mediated degradation requires phosphorylation

226 ins, which promotes CHD1 degradation via the beta-TrCP-mediated ubiquitination-proteasome pathway.

227 nd 2-deoxyglucose, we demonstrated that this beta-TrCP accumulation resulted from decreased Skp2 expr

228 Moreover, we obtained evidence that this beta-TrCP-dependent degradation takes part in controllin

229 catenin-associated E-cadherin levels through beta-TrCP-dependent stabilization of the transcriptional

230 ha and GSK3 promotes beta-catenin binding to beta-TrCP, leading to beta-catenin degradation through t

231 nics, effects that were overcome by siRNA to beta-TrCP and GSK-3beta or LPCAT1 gene transfer, respect

232 binding substrate, cdk2, can be tethered to beta-TrCP, ubiquitinated, and effectively degraded.

233 tified DSGIS(338) and DSAPGS(378) as the two beta-TrCP-binding motifs in Nrf2.

234 The ability of one of the two beta-TrCP-binding sites to serve as a degron could be bo

235 Overexpression of wild-type beta-TrCP in mammalian cells promoted the downregulation

236 Mechanisms underlying beta-TrCP regulation and their aberration in human and a

237 degradation in general, since the unrelated beta-TrCP target Snail is also stabilized by ORF61.

238 iquitination and degradation by upregulating beta-TrCP.

239 rolled at the level of protein stability via beta-TrCP-dependent, ubiquitin-based proteasomal degrada

240 rmore, USP47 deubiquitinates itself, whereas beta-TrCP promotes USP47 ubiquitination through interact

241 A forms a direct, Ras-regulated complex with beta-TrCP, the substrate recognition component of the SC

242 d an increased association of cyclin D1 with beta-TrCP, whereas no specific binding was noted with ot

243 Interaction with beta-TrCP is also necessary for ubiquitination of Ikappa

244 that partly depends on its interaction with beta-TrCP, a substrate adaptor for an SCF (Skp-Cullin 1-

245 on in Bora and promotes its interaction with beta-TrCP.

246 er demonstrate that SVV ORF61 interacts with beta-TrCP, a subunit of the SCF ubiquitin ligase complex

247 loss of the known interaction of Rassf1 with beta-TrCP that usually mediates degradation of beta-cate

248 cells increased specific binding of Sp1 with beta-TrCP.