ライフサイエンスコーパス: importin-beta

1 tic cargoes from the nuclear import receptor importin beta.

2 le-associated protein that binds directly to importin beta.

3 n binding region in the NH2-terminal half of importin beta.

4 tes, significantly expands the repertoire of importin beta.

5 n, snRNPs are transported to the nucleus via importin beta.

6 zinc finger domain, bind importin alpha and importin beta.

7 PN interacts with SMN, Gemin3, Sm snRNPs and importin beta.

8 into the nucleus by direct interaction with importin beta.

9 protein that recognizes both the TMG cap and importin beta.

10 ely mediated by the nuclear transport factor importin beta.

11 rtin alpha is only observed upon addition of importin beta.

12 is blocked by a dominant-negative mutant of importin beta.

13 , anti-NPC antibodies, or antibodies against importin beta.

14 proteins may occur through direct binding to importin beta.

15 t it can form a ternary complex with Ran and importin beta.

16 nother 90 kDa protein that was identified as importin beta.

17 inant negative versions of the GTPase Ran or importin beta.

18 idge between the NLS and the import receptor importin beta.

19 RIPalpha serves as an adaptor to link RPA to importin beta.

20 ly described import of cyclin B1 mediated by importin beta.

21 pr are major physiological binding sites for importin beta.

22 of JMY requires both the WH2/NLS region and importin beta.

23 ntains two distinct binding determinants for importin beta.

24 e major egg lamin, XLB3, importin alpha, and importin beta.

25 oporin FXFG motif binding to HEAT repeats in importin-beta.

26 or snurportin1 (SPN) and the import receptor importin-beta.

27 es is mediated primarily by carriers such as importin-beta.

28 importin-alpha, while a central domain binds importin-beta.

29 nteracted with the nuclear transport factor, importin-beta.

30 stable complex with the transport receptor, importin-beta.

31 TP but not RanGDP prevented these effects of importin-beta.

32 n or dominant interfering mutants of Ran and importin-beta.

33 capsid severely inhibited interactions with importin-beta.

34 ing site for a second nuclear import factor, importin-beta.

35 la SNUP (dSNUP) does not interact with Ketel/importin-beta.

36 he complex between the Ras homologue Ran and Importin-beta.

37 eta-catenin to a greater extent than that of importin-beta.

38 r experiments using dual-fluorophore-labeled Importin-beta.

39 ilized cell import assay we demonstrate that importin beta (1-485) can import PTHrP-coupled cargo in

40 olved the crystal structure of a fragment of importin beta-1 (1-485) bound to the nonclassical NLS of

41 Knockdown of importin beta-1 blocks targeting of CRB3-CLPI to the spi

42 ing mitosis, and a dominant-negative form of importin beta-1 closely phenocopies CRB3-CLPI knockdown.

43 Importin beta-1 colocalizes with CRB3-CLPI during mitosi

44 ation, we find that CRB3-CLPI interacts with importin beta-1 in a Ran-regulated fashion.

45 Interestingly, truncated importin beta 45-462 allows membrane fusion but produces

46 om classical nuclear import but dependent on importin beta, a component of multiple nuclear import pa

47 These receptors bear distant homology to importin beta, a subunit of the receptor for proteins wi

48 Here, we show that importin beta, a well established nucleocytoplasmic tran

49 shares a domain of significant homology with importin-beta, a cytoplasmic transport factor that inter

50 binding to Ran guanosine triphosphate (GTP)-importin-beta, accumulation of importin-beta at nuclear

51 control suggested a potential new arena for importin beta action, although it is also possible that

52 Importin beta acts positively in multiple interphase rol

53 The intrinsic structural flexibility of importin beta allows its concerted interactions with IBB

54 ur results suggest that rAAV2 interacts with importin-beta alone or in complex with other karyopherin

55 the two negative regulators, transportin and importin beta, along with the positive regulator RanGTP,

56 Excess full-length importin beta and beta 45-462 act similarly when added t

57 leoporin subunit targets for transportin and importin beta and find them to be largely the same: ELYS

58 inding (sIBB) domain to recruit the receptor importin beta and gain access to the nucleus.

59 involved in the interaction of Rb/p130 with importin beta and importin alpha, members of the nuclear

60 hSRP1 gamma can form a complex with importin beta and is able to mediate import of a BSA-NLS

61 ple device: Ran-GTP-sensitive interaction of importin beta and its cargo proteins.

62 gg extracts is regulated at least in part by importin beta and its regulator, the small GTPase, Ran.

63 ults demonstrate that MUC1-C associates with importin beta and not importin alpha.

64 he recruitment of nuclear components such as Importin beta and Nup153 in a PP1-independent manner.

65 Tpr, which has no FXFG repeats, binds to importin beta and to importin alpha/beta heterodimers, b

66 We conclude that the cell contains importin beta and transportin "global positioning system

67 The nuclear import receptors importin beta and transportin play a different role in m

68 t transport mediated by the import receptors importin beta and transportin, but not by the export rec

69 Two nuclear import pathways, mediated by importin beta and transportin, converge on a single nucl

70 least partly involves its direct binding to importin beta and transportin.

71 rved NLS motif, which then binds directly to importin beta and triggers nuclear translocation.

72 signal (NLS) at its C-terminus that binds to importin-beta and is required for cortical polarity and

73 d that Ran regulates the interaction between importin-beta and NuMA.

74 ss form ternary complexes with importin-5 or importin-beta and Ran-GTP.

75 l structure of FG-nucleoporin cores bound to importin-beta and TAP/p15 identified a number of common

76 psid proteins from rAAV2 could interact with importin-beta and that this interaction was sensitive to

77 ase, as well as to the nuclear transporters, importins-beta and exportins.

78 -regulating release of assembly factors from importin beta, and 2) direct action by transportin bindi

79 of recombinant Rch1 (human importin alpha2), importin beta, and GTPase Ran.

80 Whereas addition of purified importin alpha, importin beta, and RAN was sufficient to support protein

81 ort repeat proteins of the HEAT superfamily, importin beta, and transportin, as well as the export pr

82 of the nuclear localization signal receptor, importin-beta, and that are found in all eukaryotes from

83 uired to mediate interactions with TMG caps, importin-beta, and the export receptor, exportin1 (Xpo1/

84 RIPalpha interacts directly with recombinant importin beta as well as with RPA in vitro.

85 osphate (GTP)-importin-beta, accumulation of importin-beta at nuclear pores, and cNLS-mediated protei

86 rt that are distinct from the competition by importin-beta/beta-karyopherin and may be involved in th

87 aryopherin, indicating that beta-catenin and importin-beta/beta-karyopherin both interact with common

88 ly to the nuclear pore machinery, similar to importin-beta/beta-karyopherin or other importin-beta-li

89 Rather, docking is specifically competed by importin-beta/beta-karyopherin, indicating that beta-cat

90 Nuclear import receptors RanBP7 and importin beta bind tightly to somatic H1 but not H1M, an

91 to-inhibitory sequence within the N-terminal importin beta binding (IBB) domain of importin alpha reg

92 Recent work shows that the N-terminal importin beta binding (IBB) domain of importin alpha reg

93 urportin associate with importin beta via an importin beta binding (IBB) domain.

94 r to importin alpha, SNP1 uses an N-terminal importin beta binding (sIBB) domain to recruit the recep

95 two functions of the N-terminal IBB domain, importin beta binding and auto-inhibition.

96 port that a mutant SPN construct lacking the importin beta binding domain (IBB), but containing an in

97 in alpha5 is not displaced by the N-terminal importin beta binding domain and requires the importin a

98 ons of importin beta bound to the snurportin importin beta binding domain trapped in the same crystal

99 resent in Imp alpha, with the exception that importin beta binding is known to map close to the Imp a

100 Strikingly, a Nup153 fragment containing the importin beta binding site acted as a dominant-negative

101 However, XAP2 hinders importin beta binding to the mAhR complex, suggesting th

102 nus of importin alpha, which is displaced by importin beta binding.

103 by Cse1p:RanGTP only in the presence of the importin-beta binding (IBB) domain of Kap60p.

104 Of interest, the importin-beta binding (IBB) domain of SPN1, which is ess

105 tion of a single arginine residue within the importin-beta binding domain (IBB) disrupted the interac

106 the autoinhibitory mechanism mediated by the importin-beta binding domain of importin-alpha operates

107 Molecular recognition of the importin beta-binding (IBB) domain of importin alpha by

108 e energy of inhibition of the importin alpha importin beta-binding domain ( approximately 3 kcal/mol)

109 protein of 545 amino acids that possesses an importin-beta-binding domain and armadillo/beta-catenin-

110 ing the RanGTP-state and clamping the Kap60p importin-beta-binding domain, ensuring that only cargo-f

111 Importin beta binds directly to Nup153 and in vitro can

112 pha recognizes a NLS on a target protein and importin beta binds the nuclear pore complex.

113 d two drastically different conformations of importin beta bound to the snurportin importin beta bind

114 in coassociates with the nuclear transporter Importin beta but fails to show evidence of nuclear tran

115 domain (IBB) disrupted the interaction with importin-beta, but preserved the ability of SPN to bind

116 ed after being released from their inhibitor importin beta by Ran(GTP).

117 ogical evidence that release of Ran-GTP from importin beta by RanBP1 and importin alpha is critical f

118 and other APA components are discharged from importin beta by RanGTP and induce spindle-like structur

119 ce energy transfer signal when released from importin-beta by RanGTP.

120 Down-regulation of importin-beta by RNA interference (RNAi) efficiently abr

121 Based on these results, we suggest that importin beta can mediate the nuclear import of arginine

122 ing analysis to determine the affinity of an importin beta cargo complex for Nup358, the Nup62 comple

123 In cells, the Ran-importin-beta-cargo gradient kinetically promotes spindl

124 y, we found that hCRM1 and import factor p97/importin beta colocalized with the ectopically expressed

125 a peptide's affinity for the importin alpha-importin beta complex.

126 A Ran x GDP-RanBP1-importin-beta complex also displayed a low FRET signal.

127 olated nuclei indicates that Nup153- and Tpr-importin beta complexes exist in assembled nuclear pores

128 is able to disassemble both Nup153- and Tpr-importin beta complexes.

129 ion of RanBP2 is to capture recycling RanGTP-importin-beta complexes at cytoplasmic fibrils to allow

130 Here, we report that KPNB1, an importin beta component of the ncRNA repressor of nuclea

131 ted by at least approximately 10-fold by the importin beta concentration and therefore suggest a pote

132 At low importin beta concentrations, about half of the signal-d

133 At high importin beta concentrations, the import efficiency incr

134 independent cargo was also increased by high importin beta concentrations.

135 Importin-beta consists of 19 HEAT repeats that are based

136 Furthermore, we show that importin beta cooperates with Ran GTPase to promote ubiq

137 d particles revealed that rAAV2 localized to importin-beta-dense regions of cells in late trafficking

138 t cyclin B1 import is mediated by an unusual importin beta-dependent mechanism that does not require

139 nd exportin 1 and involved the activation of importin beta-dependent nuclear import of 53BP1, a large

140 restored RANGAP1 to kinetochores and rescued importin-beta-dependent mitotic dynamic defects.

141 5 nuclear localization, whereas knockdown of importin-beta did.

142 n), we infer that the Rex NLS interacts with importin beta directly.

143 eals a second extended cargo binding site on importin beta distinct from the IBB domain binding site.

144 These data indicate that Ketel/importin-beta does not play a significant role in Drosop

145 SAD2 was found to encode an importin beta-domain family protein likely to be involve

146 The importin beta down-regulation of membrane fusion is Ran-

147 progressively more distal binding sites for importin beta during import.

148 However, the association of p53(420) with importin-beta, essential for nuclear import, was signifi

149 C3 binds directly to the karyopherins of the importin beta family in a RanGTP-insensitive manner and

150 onclassical import pathway that utilizes the importin beta family member Pse1/Kap121.

151 e a mechanism of EGFR regulation through the importin beta family member RAN-binding protein 6 (RanBP

152 ation analyses, revealed that a nonclassical importin beta family member, IPO3, was the only importin

153 Here, we report that Msn5, a member of the importin beta family of nuclear transport receptors, is

154 extended our studies to other members of the importin-beta family and found that all tested karyopher

155 HST is one of at least 17 members of the importin-beta family in Arabidopsis and is the first mem

156 The importin-beta family members (karyopherins) mediate the

157 uding transportin 3 (TNPO3), a member of the importin-beta family of nuclear import proteins.

158 Msn5 and Los1, members of the importin-beta family, function in tRNA nuclear export.

159 rgoes and nuclear transport receptors of the importin-beta family.

160 uires Ran and the Mtr10/Kap111 member of the importin-beta family.

161 n mutant strains deficient in members of the importin-beta family.

162 factors in the karyopherin-beta (also called importin-beta) family mediate the movement of macromolec

163 eptor used by Pho4 for nuclear export is the importin-beta-family member Msn5, which is required for

164 f Rtg1 and Rtg3, whereas export requires the importin-beta-family member Msn5.

165 ition of the transport adaptor snurportin by importin beta follows the population selection mechanism

166 restingly, the arginine-rich NLS of Rex uses importin beta for import but does so by a mechanism that

167 GTP produced on chromatin frees factors from importin beta for localized assembly.

168 y approximately 200-fold reduced affinity of importin beta for Nup62, when bound to the sIBB.

169 Whereas full-length AR requires Hsp90 and importin-beta for active nuclear translocation, basal nu

170 of MKL1, which affects its interaction with Importin-beta for efficient nuclear import.

171 p153 complex, but cannot displace endogenous importin beta from a Tpr complex.

172 1 import was decreased by immunodepletion of importin beta from cytosol.

173 tazole, a small-molecule inhibitor of RanGTP/importin-beta function, to study the role of Ran in spin

174 These results reveal previously unrecognized importin-beta functions at kinetochores exerted via RANB

175 ssay, both importin 7 and the importin alpha-importin beta heterodimer could import a GR NL1 fragment

176 role in betabeta' nuclear localization: the importin beta homolog Kap122 and the WD40 repeat protein

177 Mutations in the Drosophila Importin beta homolog Ketel, also reduce the nuclear loc

178 Knockout of the closest importin beta homolog of SAD2 in Arabidopsis did not dup

179 tivity of a gene, NMD5, that encodes a novel importin beta homolog.

180 3, two integral nuclear pore components, and importin-beta IMB-1 provides strong evidence that this r

181 Imp alpha is in turn bound by importin beta (Imp beta), which targets the resultant pr

182 , replacement of CBC by eIF4E is promoted by importin beta (IMPbeta): Inhibiting the binding of IMPbe

183 Soluble karyopherins of the importin-beta (impbeta) family use RanGTP to transport c

184 Importin-beta (Impbeta) is a major transport receptor fo

185 In permeabilized cells, importin beta imports a cargo fused to the snurportin IB

186 y, we found that SMN directly interacts with importin beta in a GST-pulldown assay, suggesting that t

187 ical nuclear localization sequence, it binds importin beta in a RanGTP-regulated manner.

188 results establish an unanticipated role for importin beta in ER protein quality control.

189 cible inhibition of the conserved Drosophila importin beta in lateral neurons abolishes behavioral rh

190 egulates NLS-cargo binding in the absence of importin beta in vitro.

191 mics simulations using crystal structures of Importin-beta in its free form or in complex with nuclea

192 Our data suggest Vpr functionally resembles importin-beta in nuclear import of the HIV-1 pre-integra

193 etylation of Lys22 promoted interaction with importin-beta in vitro.

194 Moreover, overexpression of either Vpr or importin-beta in yeast blocks nuclear transport of mRNAs

195 Importin beta inhibits spindle formation in vitro and in

196 We further show that importin beta inhibits the regulatory phosphorylation of

197 We show that transportin-and importin beta-initiate their regulation as early as the

198 Co-expressing either importin-beta-interacting RANBP2 fragments, or CRM1, res

199 other serotypes and found that the extent of importin-beta interaction varied, suggesting that differ

200 Importin-beta interacts through this region with NUP358/

201 When excess importin beta is added to a full Xenopus nuclear reconst

202 In most of these, importin beta is counteracted by its regulator, Ran-GTP.

203 ta-binding (IBB) domain of importin alpha by importin beta is critical for the nuclear import of prot

204 vitro reconstitution assays demonstrate that importin beta is critically required for ubiquitination

205 That the complex of Tpr with importin beta is fundamentally different from that of Nu

206 Importin beta is known to act by repressing assembly fac

207 We show that importin-beta is an inhibitor of microtubule aster assem

208 Importin-beta is the main vector for interphase nuclear

209 etic data indicated that the binding to both importins-beta is essential for cell growth, and photobl

210 confer a low nanomolar binding affinity for importin beta (K(d) approximately 2 nm) in an interactio

211 tes with ribosome biogenesis factors and the importins-beta Kap123p and Sal3p.

212 We now show that in contrast to loss of importin beta (Kap95p/Rsl1p) and transportin (Kap104p),

213 e present the structure of full-length yeast importin-beta (Kap95p or karyopherin-beta) complexed wit

214 Human NXF1 can be imported via importin beta, karyopherin beta2, importin 4, importin 1

215 ta-arrestins (Arrbs), the small GTPase Rab5, importin-beta (Kpnb1), and transportin-1 (Tnpo1).

216 he nuclear pore without the assistance of an importin beta-like cofactor.

217 of Dcas, the Drosophila ortholog of CAS, the importin beta-like export receptor for importin alpha.

218 that HST is the Arabidopsis ortholog of the importin beta-like nucleocytoplasmic transport receptors

219 r to importin-beta/beta-karyopherin or other importin-beta-like import factors, such as transportin.

220 d members of the nuclear transport receptor (importin-beta-like) superfamily.

221 onstrate that Ran import is independent from importin-beta-mediated protein import.

222 Importin beta mediates active passage of cellular substr

223 ibition studies support the possibility that importin beta moves from Nup358 to Nup153 via the Nup62

224 l interfering RNAs (siRNAs) directed against importin-beta mRNAs, which down-regulated classical nucl

225 The results also show that, like importin beta, MUC1-C binds to Nup62 (nucleoporin p62).

226 An importin beta mutant with a combination of mutations in

227 A dominant-negative importin-beta mutant inhibited nuclear import of Ran, wh

228 We report that importin beta negatively regulates two of these events,

229 The importin beta NPC block, which maps downstream of GTPgam

230 LSs) and to mediate their recruitment to the importin beta nuclear import factor, little is known abo

231 ragment freely exchanges with the endogenous importin beta/Nup153 complex, but cannot displace endoge

232 Importin beta, once thought to be exclusively a nuclear

233 bitory function without impacting binding to importin beta or the importin alpha export receptor, Cse

234 competitive inhibitors of importin-alpha or importin-beta or by the absence of importin-alpha.

235 Microinjection of excess importin-beta or depletion of the Ran-dependent spindle

236 l pathway does not require importin-alpha or importin-beta or the addition of any other soluble facto

237 Overexpression of importin-beta, or of the nucleoporin-binding region, inh

238 , small interfering RNA (siRNA) knockdown of importin-beta partially inhibited rAAV2 nuclear transloc

239 In contrast, importin beta plays a negative regulatory role in mitoti

240 Lastly, importin beta plays a role in transducing damage signals

241 Thus, importin beta possesses two nucleoporin binding sites, b

242 Purified importin beta promoted cyclin B1 import in the absence o

243 monstrate that the Sel1L, Hrd1, p97/VCP, and importin beta proteins are required for the dislocation

244 dicate that freely diffusing importin alpha, importin beta, Ran and NTF2 are in dynamic equilibrium w

245 alyzed dynamic properties of importin alpha, importin beta, Ran and NTF2 in nucleus, cytoplasm and at

246 Recombinant importin alpha, importin beta, Ran, and NTF2 alone were sufficient to su

247 However, Ran x GTP complexes with importin-beta, RanBP1, and Crm1 all show reduced FRET co

248 zes microtubules in egg extracts in a RanGTP/importin beta-regulated manner.

249 We further find that importin beta regulates EGFR nuclear transport to the IN

250 This suggests a novel mechanism by which importin beta regulates the activity of a spindle assemb

251 Here we show that importin-beta regulates multiple aspects of mitosis via

252 This reveals distinct importin beta-regulation of NPC assembly.

253 on, although it is also possible that one of importin beta's relatives, the karyopherin family of pro

254 Consistently, in vivo, the importin beta.sIBB complex has greatly reduced persisten

255 Knockdown of importin beta specifically inhibited the degradation of

256 t tether NLS-containing proteins to the p97/ importin beta subunit and to the downstream transport ma

257 recognizes classical NLS sequences, and the importin beta subunit directs the complex to the nuclear

258 Like the importin-beta subunit of the nuclear import receptor, Vp

259 nts, including a mutation of a member of the importin beta superfamily, inhibits Npl3p reimport from

260 in, which could have evolved into the modern importin beta superfamily.

261 h multiple proteins including members of the importin-beta superfamily and likely functions as a spec

262 lear envelope most frequently by karyopherin/importin-beta superfamily members that are constructed f

263 The Ran-importin-beta system also functions in mitotic spindle a

264 describe how microtubules and the RAN GTPase/importin-beta system collaborate to control timing of HU

265 Here we examine the Ran-importin-beta system in cells by conventional and fluore

266 Furthermore, a dominant negative importin beta that inhibits nuclear transport, also prev

267 t is mediated mainly by the transport factor importin-beta that binds cytoplasmic cargo, most often v

268 teraction with a site in the NH2 terminus of importin-beta that is distinct from that used to bind im

269 d by the domain of importin alpha that binds importin beta (the IBB domain), we infer that the Rex NL

270 Transport of Kap95p (yeast importin-beta), the principal carrier for protein import

271 egree of strain in the tertiary structure of importin beta, the IBB domain modulates the affinity of

272 Additionally, binding of cyclin B1 to importin-beta, the factor known to be responsible for th

273 Importin-beta, the second subunit of the NLS receptor co

274 icated that vertebrate snRNP import requires importin-beta, the transport receptor that binds directl

275 Importin beta then binds to the importin alpha-Rb2/p130

276 Importin-beta therefore links NuMA to regulation by Ran.

277 The C terminus binds importin-beta through RanGTP.

278 region reduce the nuclear import activity of importin beta to a similar extent ( approximately 50%).

279 ortin alpha is critical for the recycling of importin beta to a transport-competent state.

280 clear import receptors importin alpha and/or importin beta to control the sequestration of proteins n

281 We propose that a precise balance of importin beta to Ran is required to create a correct dou

282 mpede the export of tRNA or the recycling of importin beta to the cytoplasm.

283 ; this heterodimer then forms a complex with importin-beta to interact with the nuclear pore complex.

284 nuclear transport receptors (NTRs), NTF2 and Importin beta, together with the concomitant film thickn

285 Our results indicate that the importin beta transport complex binds to nucleoporins wi

286 family, which can bind cargo directly (e.g., importin-beta, transportin-1, transportin-3, importin-13

287 equence similarity to several members of the importin beta/transportin family.

288 he function of four conserved tryptophans of importin beta (Trp-342, Trp-430, Trp-472, and Trp-864) l

289 We propose that importin beta uses the tryptophans to select and stabili

290 importin alpha and snurportin associate with importin beta via an importin beta binding (IBB) domain.

291 ion by importin alpha, which associates with importin beta via the IBB domain.

292 hermore, in the absence of cytosol, purified importin beta was both sufficient and necessary to suppo

293 Kap95 (importin-beta) was necessary for nuclear entry, but not

294 s as the NLS receptor, and karyopherin beta1/importin beta, which binds karyopherin alpha and mediate

295 rted into the nucleus by the import receptor importin beta, which binds to cargoes via the adaptor im

296 ain displays significant specific binding to importin beta, which is diminished or eliminated by muta

297 Smad 3 exhibits weak but specific binding to importin beta, which is enhanced after phosphorylation b

298 receptor consisting of the beta-karyopherin importin beta, which mediates interactions with the nucl

299 T/RNA/Impalpha complexes were dissociated by importin-beta, which also blocked the stimulation of cap

300 the nuclear pore complex by interactions of importin beta with a series of nucleoporins.