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

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

11 rafficking elements into the lethal antihost Nup phosphorylation pathways.

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

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

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

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

16 ubcomplex with the oncogenic nucleoporin CAN/Nup 214.

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

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

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

20 aries between scaffold and transport-channel Nups.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

40 t pathways in cells expressing the mutant FG Nups.

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

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

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

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

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

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

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

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

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

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

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

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

53 The FG Nups interact promiscuously with various nuclear transpo

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

79 84-120 complex and identified two new fungal Nups, An-Nup37 and An-ELYS, previously thought to be ver

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

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

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

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

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

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

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

87 regulatory steps are controlled by metazoan Nups remains unclear.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

104 ple copies of approximately 30 nucleoporins (Nups).

105 y 30 different proteins called nucleoporins (Nups).

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

144 30 different proteins called nucleoporins or Nups.

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

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

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

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

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

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

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

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

153 plasmically and nucleoplasmically positioned Nups.

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

155 perphosphorylation of nuclear pore proteins (Nup).

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

171 equences that act differentially on specific Nups.

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

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

174 04 and B52 proteases preferentially targeted Nups in the import pathways, while B04 and C15 proteases

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

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

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

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

179 essential without the An-Ndc1 transmembrane Nup.

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

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

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