ライフサイエンスコーパス: Nup

1 Nup-358 is a giant nucleoporin located at the tips of th

2 Nups play an evolutionarily conserved role in gene expre

3 Nups were mislocalized in adult intestinal nuclei and in

4 We previously found that nucleoporin 153 (Nup 153) is required for timely progression through late

5 that, due to unfavorable entropy changes, a Nup-Dyn2 complex with three Dyn2 dimers is more stable t

6 t others (NSP1, Nup116, and Nup1), forming a Nup/Crm1/RanGTP complex and concomitantly releasing Rev.

7 o Nup107Nup133-depleted NPCs, whereas p62, a Nup at the center of the NPC, was unaffected.

8 Among the affected Nups was a member of the Nup107 subcomplex, Nup133, wher

9 We discovered that, although all Nups display uniformly slow turnover, their exchange rat

10 geting of the pore basket components Tpr and Nup 50 in midbody-stage cells.

11 Crm1 and Nups co-occupy enhancers, and Crm1 inhibition blocks int

12 etics using eIF4G from cellular extracts and Nups presented in native (NPC) or recombinant formats.

13 aberrant interaction between mutant FUS and Nups is underscored by studies in Drosophila, whereby re

14 FUS and Nups were found to interact independently of RNA in cell

15 investigate the functional roles of NPCs and Nups in transcription, chromatin organization, and epige

16 We find that, in young non-stressed animals, Nup foci only appear in developing sperm, oocytes and em

17 rafficking elements into the lethal antihost Nup phosphorylation pathways.

18 kdown of CHMP7 alleviated disease-associated Nup alterations, deficits in Ran GTPase localization, de

19 We propose that this Sir4-associated Nup complex is distinct from holo-NPCs and that it plays

20 p-cargo complexes to Nup1p (a nuclear basket Nup) is 225-fold higher than to Nup100p (a central scaff

21 ription factors mediate interactions between Nups and enhancers and promoters.

22 U0126 and SB203580) were sufficient to block Nup hyperphosphorylation in EMCV-infected or L-expressin

23 y comprised of ~30 different proteins called Nups that mediates selective macromolecular transport be

24 y introducing the nuclear-localized cameleon Nup-YC2.1 into Casuarina glauca we show that cell-free c

25 ubcomplex with the oncogenic nucleoporin CAN/Nup 214.

26 r pore complex until RanGTP severs the cargo-Nup bonds to effect release into the nucleus.

27 Additionally, in proliferative cells, Nups play a crucial role in genome integrity maintenance

28 Nup62 is a central channel Nup that has a prominent role in forming the selectivity

29 scaffold is decorated with transport-channel Nups that often contain phenylalanine-repeat sequences a

30 aries between scaffold and transport-channel Nups.

31 Nuclear pore complex components (Nups) have been implicated in transcriptional regulation

32 chanisms by which individual NPC components (Nups) participate in the regulation of these pathways re

33 exchange slowly, whereas flexible connector Nups threading throughout the NPC architecture exchange

34 eral phenylalanine-glycine repeat-containing Nups that serve as docking sites for karyopherins.

35 chanism driven by indel accumulation in core Nup promoters.

36 on of Nup upstream regions reveals that core Nup complex gene promoters accumulate indels rapidly.

37 the composition and incidence of cytoplasmic Nup foci in an intact animal, C. elegans.

38 Timely localization of the cytoplasmic Nup transport factor fragile X-related protein 1 (FXR1)

39 encephalomyocarditis virus (EMCV) L-directed Nup phosphorylation were screened with a panel of specif

40 Thus, we argue that directed Nup-mediated molecular motion may represent an intrinsic

41 Further, unlike other dispersed Nups, An-Nup2 locates exclusively to mitotic chromatin,

42 pe and acts as a scaffold to which dispersed Nups return during mitotic exit.

43 RanBP1 (or homologous proteins) can displace Nup and form a ternary RanBP1/RanGTP/Crm1 complex that c

44 e show that ectopically tethering Drosophila Nups, especially Sec13, to chromatin is sufficient to in

45 One such dynamic Nup, called Nup98, has been implicated in gene activatio

46 , but there are also novel roles for dynamic Nups within the nucleoplasmic compartment.

47 change rate was relatively unrelated to each Nup's position, accessibility, or role in transport but

48 ely on the specific combination of essential Nups located in the central plane of the NPC.

49 use surface plasmon resonance to evaluate FG Nup conformation, binding equilibria, and interaction ki

50 t channel, it is unclear how this impacts FG Nup barrier function or the movement of other molecules,

51 omoted by alterations in the barrier-like FG Nup conformations.

52 cilitate transport by partitioning in the FG Nup assembly, overcoming the barrier by their affinity t

53 ed phases of NTF2 and Imp-beta within the FG Nup assembly.

54 odulates how the other NTR penetrates the FG Nup assembly.

55 he structural properties of S. cerevisiae FG Nups by using biophysical methods and predictive amino a

56 Certain FG Nups are believed to associate via low-affinity, cohesiv

57 eta1 (Kapbeta1) binding to four different FG Nups.

58 ein interactions that occur at individual FG Nups were sampled using immobilized nucleoporins and yea

59 nsitivity assays to demonstrate that most FG Nups are disordered in situ within the NPCs of purified

60 phenylalanine-glycine (FG)-repeat motifs (FG Nups).

61 t pathways in cells expressing the mutant FG Nups.

62 dered phenylalanine-glycine nucleoporins (FG Nups) that guard the NPC channel.

63 nsically disordered Phe-Gly nucleoporins (FG Nups) within nuclear pore complexes exert multivalent in

64 a1 to phenylalanine-glycine nucleoporins (FG Nups), which is comparable with RanGTP.Kapbeta1, but str

65 ed of phenylalanine-glycine nucleoporins (FG Nups)--intrinsically disordered proteins that facilitate

66 dered phenylalanine-glycine nucleoporins (FG Nups).

67 to limited binding with the pre-occupied FG Nups at physiological Kapbeta1 concentrations.

68 -beta), to different planar assemblies of FG Nups, with the binding behaviour defined by negative coo

69 As binding sites for transport receptors, FG Nups are critical in translocation through the NPC.

70 eoporins that contain FG peptide repeats (FG Nups) are proposed to function as stepping stones in kar

71 ch contain phenylalanine-glycine repeats (FG Nups) that bind karyopherins and facilitate the transpor

72 enylalanine-glycine (FG) peptide repeats (FG Nups).

73 The conclusion that FG Nups constitute a family of natively unfolded proteins s

74 We find that FG Nups, particularly the large FG repeat regions, exhibit

75 Therefore, the FG Nups are necessary but insufficient for NPC barrier func

76 a minimal physical model that treated the FG Nups as flexible homopolymers and the NTRs as uniformly

77 ever, the strong binding of Kaps with the FG Nups due to avidity contradicts rapid Kap translocation

78 The FG Nups interact promiscuously with various nuclear transpo

79 We conclude that the FG Nups resemble stimuli-responsive molecular 'velcro', whi

80 forms an integral constituent within the FG Nups that coexists with a fast phase, which dominates tr

81 ming the barrier by their affinity to the FG Nups, and comprise a significant fraction of proteins in

82 promiscuous binding interactions with the FG Nups, which enable CRM1 to compensate for the loss of Ka

83 We find that many proteins bind to FG Nups in highly reproducible patterns.

84 Although the binding of NTRs to FG Nups increases molecular crowding in the NPC transport c

85 asured the apparent affinity of Kap95p to FG Nups representing three distinct regions of the S. cerev

86 ; exportins exhibited enhanced binding to FG Nups, and importins exhibited reduced binding.

87 tionally, we study phase separation in an FG-Nup mixture that resembles the NPC stoichiometry and obs

88 nance, we show that a rapidly fluctuating FG-Nup populates an ensemble of conformations that are pron

89 for recruiting the transport factors for FG-Nup and RanGTP-dependent transport through the NPC.

90 FG interactions, similar to the homotypic FG-Nup condensates.

91 o large capsids were excluded from liquid FG-Nup droplets, but functional import complexes underwent

92 s that are essential for the formation of FG-Nup condensates featuring droplet-spanning percolated ne

93 Only a minor fraction of FG-Nup molecules concentrate in Nup foci, which dissolve du

94 phenylalanine-glycine nucleopore protein (FG-Nup) structure, flexibility, and cross-linking.

95 ncing age, and overexpression of a single FG-Nup in post-mitotic neurons is sufficient to induce ecto

96 when engaging with the NTR, allowing the FG-Nup to maintain an unexpectedly high plasticity in its b

97 like other transport receptors, contacts FG-Nups via multiple binding sites.

98 phase separation behavior, the different FG-Nups of the yeast NPC can be divided into two classes: T

99 The intrinsically disordered FG-Nups in the central channel of the nuclear pore complex

100 characteristics of each of the disordered FG-Nups of the yeast NPC.

101 llance of native intrinsically disordered FG-Nups.

102 How FG-Nups are protected from making inappropriate interaction

103 phenylalanine-glycine-rich nucleoporins (FG-Nups) that regulate the selective passage of biomolecule

104 phenylalanine-glycine-rich nucleoporins (FG-Nups) to control nucleocytoplasmic transport.

105 hesive FG repeat-containing nucleoporins (FG-Nups), which are maintained near their solubility limit

106 phenylalanine/glycine-rich nucleoporins (FG-Nups), which form a permeability barrier of still elusiv

107 phenylalanine-glycine-rich nucleoporins (FG-Nups).

108 ered liquid-to-liquid phase separation of FG-Nups, which yielded droplets that showed typical propert

109 FG-FG interactions, while the peripheral FG-Nups (mostly FxFG-type) at the entry and exit of the NPC

110 opherin complex remains bound to the same FG-Nups for its entire trajectory through the nuclear pore

111 e aggregation of the FG region of several FG-Nups in cells and in vitro.

112 In vitro experiments have shown that some FG-Nups can undergo phase separation into condensates that

113 NPC can be divided into two classes: The FG-Nups (mostly GLFG-type) located in the central channel o

114 ce-structure-function relationship of the FG-Nups and provides a picture of nucleocytoplasmic mass ex

115 The FG-Nups are intrinsically disordered and prone to liquid-li

116 eta1, a major transport receptor) and the FG-Nups gradually increases from both sides of the NPC and

117 teraction-dependent reorganization of the FG-Nups in the presence of the translocating particle.

118 ends more on the interaction sites of the FG-Nups than on the NPC architecture.

119 domains of the nucleoporin proteins (the FG-Nups), which control selective transport through the por

120 m the specific charge distribution of the FG-Nups, is predicted to be negative close to pore walls an

121 mational, and acid-base properties of the FG-Nups.

122 ions between a transport receptor and the FG-Nups.

123 We find that DNAJB6 binds to FG-Nups and can prevent the aggregation of the FG region of

124 with weak and transient interactions with FG-Nups, such as importin-beta.

125 igher than to Nup42p (a cytoplasmic filament Nup), revealing a steep gradient of affinity for Kap95p

126 For Nup substrates, 5 of the 6 enzymes had unique product pr

127 several model organisms provide credence for Nup functions in transcription, mRNA export, and genome

128 highlight new and unpredicted mechanisms for Nup impacts on transcription and questions that are left

129 ed recombinant enzyme (K(m) = 1.2 microM for Nup 62; K(m) = 0.5 microM for UDP-GlcNAc) are nearly ide

130 d with its structural role; scaffold-forming Nups exchange slowly, whereas flexible connector Nups th

131 84-120 complex and identified two new fungal Nups, An-Nup37 and An-ELYS, previously thought to be ver

132 FUS-Nup interactions were not localized to nuclear pores, bu

133 itated by interactions between Gag3 and GLFG Nups and that nuclear entry of the preintegration comple

134 ough NanoTraps composed of FxFG but not GLFG Nups.

135 ondensate is formed containing multiple GLFG-Nups.

136 We find that GLFG-Nups undergo phase separation and reveal that the FG mot

137 Analysis of the hyperphosphorylated Nup species revealed only phosphoserine and phosphothreo

138 Together, our data identify Nups as a class of architectural proteins for enhancers

139 ed in neural development, and alterations in Nup genes are linked to human neurological diseases.

140 fraction of FG-Nup molecules concentrate in Nup foci, which dissolve during M phase and are dispensa

141 However, the specific roles of individual Nups are poorly understood.

142 NPCs containing Nup82p (an Nsp1p-interacting Nup) were transferred to the daughter cells while functi

143 tion or expression of a dominant-interfering Nup 153 fragment results in dramatic mistargeting of the

144 indicate that Nup107 functions as a keystone Nup that is required for the assembly of a subset of Nup

145 cause no high-resolution models of X. laevis Nups were available.

146 ta support a role for altered CHMP7-mediated Nup homeostasis as a prominent initiating pathological m

147 mitotic NPC structure consisting of membrane Nups, all components of the An-Nup84 subcomplex, An-Nup1

148 regulatory steps are controlled by metazoan Nups remains unclear.

149 Here we show that Nup50 is a mobile Nup with a pronounced presence both at the NPC and in th

150 We identified the presence of multiple Nups at promoters, enhancers, and insulators in the Dros

151 The mutant Nups localize properly within the NPC and exhibit exchan

152 NUP1 These mutants were referred to as nle (Nup-lethal) mutants.

153 strate a requirement for a torsin for normal Nup localization and function and suggest that these fun

154 This identified the nucleoporin Nup 50 (Npap60) as the major full-length interacting pro

155 S led to a reduction in NCT and nucleoporin (Nup) density within the nuclear membrane of human neuron

156 the phenylalanine-glycine (FG) nucleoporin (Nup) barrier unless molecules are chaperoned by transpor

157 The mammalian nucleoporin (Nup)-107 is part of a hetero-oligomeric complex, that al

158 ed variant of the transmembrane nucleoporin (Nup) Pom121 (named sPom121, for "soluble Pom121") that a

159 evidence that the transmembrane nucleoporin (Nup), POM121, but not the Nup107-160 complex, is present

160 NTF2 domain bears at least two nucleoporin (Nup) binding pockets necessary for the colocalization of

161 rise 50 to 100 proteins termed nucleoporins (Nup).

162 Nucleoporins (Nups) are a family of proteins best known as the constit

163 Nucleoporins (Nups) are involved in neural development, and alteration

164 Nucleoporins (Nups) assemble nuclear pores that form the permeability

165 for upregulating 18 of the ~30 nucleoporins (Nups) that compose the nucleopore complex (NPC), promoti

166 evisiae NPC is comprised of 30 nucleoporins (Nups), 13 of which contain phenylalanine-glycine repeats

167 Of approximately 30 nucleoporins (Nups), 15 are structured and form the Y and inner-ring c

168 They are formed by about 30 nucleoporins (Nups), which can be roughly categorized into those formi

169 ple copies of approximately 30 nucleoporins (Nups).

170 ng a group of oocyte genes and nucleoporins (Nups).

171 vidual NPC components known as nucleoporins (Nups).

172 y 30 different proteins called nucleoporins (Nups).

173 Alterations in the components [nucleoporins (Nups)] and function of the nuclear pore complex (NPC) ha

174 e and built from ~30 different nucleoporins (Nups) in multiple copies, few are integral membrane prot

175 ltiple copies of ~30 different nucleoporins (Nups), the NPC acts as a selective portal, interacting w

176 Intrinsically disordered nucleoporins (Nups) form a selective filter inside the NPC, taking a c

177 Although most FG nucleoporins (Nups) are organized symmetrically about the planar axis

178 However, how nucleoporins (Nups) exert this control remains poorly understood.

179 (NPC) is composed of multiple nucleoporins (Nups).

180 ooc-5-mutant germ cell nuclei, nucleoporins (Nups) were mislocalized in large plaques beginning at me

181 es have shown that a subset of nucleoporins (Nups) can detach from the nuclear pore complex and move

182 diating transport, a subset of nucleoporins (Nups) engage in transcriptional activation and elongatio

183 hrough hierarchical binding of nucleoporins (Nups) forming distinct subcomplexes.

184 als that revealed how a hub of nucleoporins (Nups) in the nuclear ring binds to basket-forming Mlp/Tp

185 cells, and how malfunction of nucleoporins (Nups) might contribute to the pathogenesis of various ne

186 ave unveiled a full catalog of nucleoporins (Nups) that comprise the NPC, structural arrangements of

187 l changes to select domains of nucleoporins (Nups) within the inner ring (Nup54, Nup58, Nup62) when t

188 proximately 30 proteins termed nucleoporins (Nups), mediates selective nucleocytoplasmic trafficking.

189 me NPC components, such as the nucleoporins (Nups) Nup98 and Nup96, are also associated with the nucl

190 growth, and a subset of their nucleoporins (Nups), those that are primarily components of the cytopl

191 NPCs lacking these nucleoporins (Nups) were blocked from entry into the daughter by a put

192 after infection when all three nucleoporins (Nups) were cleaved.

193 he NPC channels are lined with nucleoporins (Nups) with extended FG (Phe-Gly) motif repeat domains, f

194 s the NPC via interaction with nucleoporins (Nups), and dissociation of the complex in the nucleoplas

195 hich makes direct contact with nucleoporins (Nups).

196 Nuclear pore proteins (nucleoporins [Nups]) physically interact with hundreds of chromosomal

197 within nuclear pore proteins (nucleoporins [Nups]), including Nup62, Nup98, and Nup153.

198 of approximately 30 proteins (nucleoporins [Nups]).

199 Many NPC proteins (nucleoporins, Nups) are modified by phosphorylation.

200 Depletion of Nup 50 is also sufficient to increase the number of midb

201 In this study, we report that disruption of Nup 153 function by either small interfering RNA-mediate

202 , suggesting that most of the RBH domains of Nup-358 are situated closer to the central axis of the N

203 Thus, the RBH and the zinc finger domains of Nup-358 were identified as two different classes of Ran-

204 m human motor cortex before the emergence of Nup alterations.

205 Comprehensive examination of Nup upstream regions reveals that core Nup complex gene

206 on, but whether this is a general feature of Nup genes has not been determined.

207 Using three recombinant fragments of Nup-358 that comprise two of the RBH domains and the zin

208 species, suggesting convergent innovation of Nup-mediated transcription regulation during mammalian e

209 nzymes had unique product profiles (order of Nup selection) or reacted at different sites within Nup6

210 but is correlated with robust recruitment of Nup Elys.

211 The underlying mechanism and regulation of Nup mobility on and off nuclear pores remain unclear.

212 ort a model whereby the selective removal of Nup FG repeat domains leads to increased NPC permeabilit

213 comprise the NPC, structural arrangements of Nups in the nuclear pore, and mechanisms of nucleocytopl

214 ins, we showed that specific combinations of Nups, especially with Nup100, but not the total mass of

215 Consistent with a functional disruption of Nups, ooc-5-mutant embryos displayed impaired nuclear im

216 Here we discuss genome-related functions of Nups and their impact on essential DNA metabolism proces

217 Importantly, this group of Nups is largely restricted to members of the inner and o

218 tion and restored the proper localization of Nups that had accumulated in cytoplasmic foci upon a shi

219 actors in a well-defined sequential order of Nups assembly onto NE during interphase.

220 is activation and for the phosphorylation of Nups, suggesting that the phenomena are linked.

221 These data indicate redundancy of Nups in the function of the mammalian NPC.

222 the hypothesis that the FG repeat regions of Nups form a meshwork of random coils at the NPC through

223 is required for the assembly of a subset of Nups into the NPC.

224 Unexpectedly, one Nup binding pocket is formed at the heterodimer interfac

225 on of nuclear pore proteins (nucleoporins or Nups), including Nup62, Nup153, and Nup214, is central t

226 a subset of NPC components (nucleoporins or Nups).

227 30 different proteins called nucleoporins or Nups.

228 gene expression due to the loss of SETDB1 or Nups results in the loss of oocyte identity, cell death,

229 omposed of proteins termed nucleoporins (or "Nups"), and (2) nuclear transport factors that recognize

230 leoporin Nup1p (t(12) < or = 21 s) and other Nups.

231 tion caused codepletion of a subset of other Nups on their protein but not on their mRNA level.

232 Nup107 and the accompanying effects on other Nups, there was no significant effect on the growth rate

233 e of karyopherin receptor prefers particular Nups or uses a limited cohort of binding motifs within t

234 Unexpectedly, one predicted peripheral Nup, Gle1, remains at the mitotic NE via an unknown mech

235 the transient proteolysis of four peripheral Nups and one transmembrane Nup.

236 that during mitosis 14 predicted peripheral Nups, including all FG repeat Nups, disperse throughout

237 eraction between Upf1p and the nuclear pore (Nup) proteins, Nup100p and Nup116p.

238 plasmically and nucleoplasmically positioned Nups.

239 which increases membrane fluidity, prevented Nup mislocalization and restored the proper localization

240 perphosphorylation of nuclear pore proteins (Nup).

241 totic disassembly such that 12 NPC proteins (Nups) form a core structure anchored across the nuclear

242 imaging of endogenously tagged NPC proteins (Nups) revealed that during mitosis 14 predicted peripher

243 ipheral nuclear pore complex (NPC) proteins (Nups) disperse from the core NPC structure.

244 teolyze nuclear pore complex (NPC) proteins (Nups) during infection, leading to disruption of host nu

245 Nucleoporin proteins (Nups) have been proposed to mediate spatial and temporal

246 of Phe/Gly-containing nucleoporin proteins (Nups) within nuclear pore complexes (NPC).

247 and cleavage of select nucleoporin proteins (Nups) within nuclear pore complexes (NPCs) to disrupt ka

248 lizes with RanGAP and nuclear pore proteins (Nups) and stabilizes the latter.

249 Nuclear pore proteins (Nups) interact with chromosomes to regulate gene express

250 Nuclear pore proteins (Nups) prominently are among the few genes linked to spec

251 The interaction of nuclear pore proteins (Nups) with active genes can promote their transcription.

252 ultiple copies of ~30 nuclear pore proteins (Nups).

253 ed by studies in Drosophila, whereby reduced Nup expression rescued multiple toxic FUS-induced phenot

254 ted peripheral Nups, including all FG repeat Nups, disperse throughout the cell.

255 Unexpectedly, the same Nups also captured the hexameric Nup84p complex and Nup2

256 d higher than to Nup100p (a central scaffold Nup) and 4000-fold higher than to Nup42p (a cytoplasmic

257 manner with Nup188, a nonessential scaffold Nup, to stabilize critical interactions within the NPC s

258 G repeats directly bind to multiple scaffold Nups in vitro and act as NPC-targeting determinants in v

259 Previous studies have shown that several Nups exhibit cell-type-specific expression and that muta

260 Recent evidence suggests that several Nups have additional roles in controlling the activation

261 This provides evidence that some Nups can acquire specialised roles in tissue-specific co

262 However, physiological functions of specific Nups and the underlying mechanisms involved in these pro

263 equences that act differentially on specific Nups.

264 cerevisiae as a model, we find that specific Nups and transport events regulate longevity independent

265 Surprisingly, Nups are not only involved in transcriptional events tha

266 04 and B52 proteases preferentially targeted Nups in the import pathways, while B04 and C15 proteases

267 We hypothesized that Nup alterations and the consequential loss of NPC functi

268 We speculate that Nup foci are non-essential and potentially toxic condens

269 One-third of these Nups contain phenylalanine-glycine (FG)-rich repeats, fo

270 The upregulation of these Nups during differentiation is crucial for NPC formation

271 imited cohort of binding motifs within those Nups, the consequences of individual 2A(pro) avidities c

272 we show that both RanGDP and RanGTP bind to Nup-358 in vitro.

273 mal titration calorimetry of Dyn2 binding to Nup constructs of increasing lengths determine that the

274 s perturbed and no conformational changes to Nups elsewhere in the NPC.

275 essential without the An-Ndc1 transmembrane Nup.

276 f four peripheral Nups and one transmembrane Nup.

277 lls devoid of all known fungal transmembrane Nups (An-Ndc1, An-Pom152, and An-Pom34) are viable but t

278 biting the nuclear export of CHMP7 triggered Nup reduction and TDP-43 dysfunction and pathology in hu

279 Here we show that two Nups of the inner channel, Nup54 and Nup58, are essentia

280 ine 4 (H3K4me2) and physically interact with Nups and a poised form of RNA polymerase II.

281 During cell division, Y-Nup-containing GLFG bodies are disassembled in mitotic p