ライフサイエンスコーパス: emerin

1 ses relocalization of the LEM domain protein emerin.

2 -relevant and inhibited by direct binding to emerin.

3 in), and is feedback-regulated by binding to emerin.

4 f viral cDNA with chromatin was dependent on emerin.

5 an essential enzyme, controls two regions in emerin.

6 the nuclear envelope proteins lamin A/C and emerin.

7 ssociated polypeptide1 (LAP1) interacts with emerin.

8 of MAN1 for binding to selected partners of emerin.

9 ys showed that MAN1-N also bound directly to emerin.

10 lamin B1, supporting functional overlap with emerin.

11 s that Ce-MAN1 overlaps functionally with Ce-emerin.

12 stitution or disease-associated mutations in emerin.

13 this pathology is worsened in the absence of emerin.

14 those required for direct binding to DNA or emerin.

15 uclear membrane proteins, including LAP2 and emerin.

16 proteins lamina-associated polypeptide 2 and emerin.

17 ble flow was nondirectional in cells lacking emerin.

18 expressing high levels of dominant-negative emerin.

19 lphaII-spectrin and NMI interact stably with emerin.

20 sociation with the native LEM-domain protein emerin, a conserved component of nuclear "lamina" struct

21 X-linked EDMD results from mutations in emerin, a lamin A-associated protein.

22 Many regions of human MAN1 are homologous to emerin, a LEM domain nuclear protein, loss of which caus

23 Emerin, a membrane component of nuclear "lamina" network

24 chor TAN lines, prompting us to test whether emerin, a nuclear membrane protein that interacts with l

25 y (X-EDMD) is inherited through mutations in emerin, a nuclear membrane protein.

26 We separated two populations of emerin, A-type lamins and BAF; one population solubilize

27 Life span was unaffected by loss of Ce-emerin alone but was significantly reduced in LEM-2-null

28 plicative myoblasts lacking A-type lamins or emerin also have decreased levels of proteins important

29 These include the mislocalization of emerin, an inner nuclear membrane protein, defects in wh

30 Here we show that emerin, an integral inner-nuclear-envelope protein, is n

31 r dystrophy is caused by loss of function of emerin, an integral protein of the inner nuclear membran

32 Emerin and A-type lamins are proteins of the inner membr

33 Emerin and BAF associated only in histone- and lamin-B-c

34 n properties and immunolocalization, both Ce-emerin and Ce-MAN1 are integral membrane proteins locali

35 Ce-emerin and Ce-MAN1 migrate on SDS-PAGE as 17- and 52-kDa

36 are essential for cell division and that Ce-emerin and Ce-MAN1 share at least one and possibly multi

37 uired for the association of viral cDNA with emerin and for the ability of emerin to support virus in

38 Additionally, emerin and lamin A are also required to maintain nuclear

39 Emerin and lamin A are implicated in regulating muscle-

40 residue) vertebrate proteins associated with emerin and lamin A at the nuclear envelope of muscle cel

41 Mutations in the nuclear envelope proteins emerin and lamin A cause a number of diseases including

42 er-4 phosphorylation inhibits BAF binding to emerin and lamin A, and thereby weakens emerin-lamin int

43 es for the nuclear membrane/lamina proteins, emerin and lamin A/C.

44 al proteins at the nuclear membrane, such as emerin and lamin AC, cause muscular dystrophy and cardio

45 t functions, for example in the targeting of emerin and lamin C to the nuclear envelope.

46 The human nuclear envelope proteins emerin and lamina-associated polypeptide 2alpha (LAP2alp

47 ric, spectrin-repeat proteins that bind both emerin and lamins A/C and form a network in muscle linki

48 g the inner nuclear membrane (INM) proteins, emerin and lamins A/C.

49 We thus conclude that emerin and LAP2alpha are not required for the early repl

50 from emerin knockout, LAP2alpha knockout, or emerin and LAP2alpha double knockout mice to be comparab

51 ittermate-derived MEFs, indicating that both emerin and LAP2alpha were dispensable for HIV-1 and MLV

52 ice deficient for emerin, LAP2alpha, or both emerin and LAP2alpha.

53 Emerin and LEM2 are ubiquitous inner nuclear membrane pr

54 To test the roles of emerin and LEM2 in somatic cells, we used null alleles o

55 This supports a model where emerin and MAN1 are at least partly retained in the inne

56 Emerin and MAN1 are LEM domain-containing integral membr

57 Emerin and MAN1 homologs are both conserved in Caenorhab

58 The nuclear envelope proteins LAP2, emerin and MAN1 share a conserved approximately 40-resid

59 We show that emerin and MAN1, but not LBR, are more mobile in the inn

60 lamin A, and transcription regulators, plus emerin and other LEM-domain nuclear proteins.

61 1 interacts physically and functionally with emerin and plays an essential and selective role in skel

62 in (Em(LEM)) of the nuclear envelope protein emerin and plays an essential role in the nuclear archit

63 Emerin and pUL34 interact physically, as shown by pull-d

64 ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, inclu

65 morphology defects and specific patterns of emerin and SUN2 mislocalization.

66 morphological changes and mislocalization of emerin and SUN2 observed in patient fibroblasts.

67 Specific binding between emerin and the functional C-terminal domain of YT521-B w

68 nfection causes a loss of connection between emerin and the lamina.

69 rk has identified nuclear envelope proteins--emerin and the linker of the nucleoskeleton and cytoskel

70 TAN lines formed normally in cells lacking emerin and were coordinated with the erratic nuclear mov

71 egulates many EDMD-relevant genes (including emerin), and is feedback-regulated by binding to emerin.

72 n IIB specifically coimmunoprecipitated with emerin, and emerin depletion prevented myosin IIB locali

73 We analyzed emr-l, which encodes Ce-emerin, and lem-2, which encodes Ce-MAN1.

74 Mutations in EMD, encoding emerin, and LMNA, encoding A-type lamins, respectively,

75 s is defined by an approximately 40-aa LAP2, Emerin, and MAN1 (LEM) domain (LEM-D) that binds the non

76 y to LEM domain nuclear proteins (e.g. LAP2, Emerin, and MAN1), lamin A, homeodomain transcription fa

77 ly binds 21 known partners, including actin, emerin, and SREBP1, but how these interactions are regul

78 nked recessive loss-of-function mutations of emerin, another component of the inner nuclear lamina th

79 However, in the absence of Ce-emerin, approximately 90% reduction of Ce-MAN1 was letha

80 The LEM domain and central region of emerin are essential for binding to BAF and lamin A, res

81 The functions of emerin are poorly understood, but EDMD affects mainly sk

82 a human heart cDNA library, with full-length emerin as bait.

83 antibodies against emerin to affinity-purify emerin-associated protein complexes from HeLa cells and

84 ion specifically and selectively reduced GFP-emerin association with BAF by 58% and also increased GF

85 in the second region, is proposed to promote emerin association with BAF in the chromatin/lamin B "ni

86 P4 cells following potent down-regulation of emerin, BAF, or LAP2alpha protein by using short interfe

87 , after affinity purification against a pure-emerin band on a western blot, it stained only the nucle

88 In cells infected with wild-type virus, emerin becomes more mobile in the nuclear membrane, and

89 Emerin belongs to the "LEM domain" family of nuclear pro

90 Emerin binding stimulated the catalytic activity of HDAC

91 l, wild-type BAF but not mutant S4E enhanced emerin binding to lamin A in vitro.

92 -Dreifuss muscular dystrophy by showing that emerin binds directly to a transcriptional repressor, GC

93 Here we show that emerin binds directly to HDAC3, the catalytic subunit of

94 We now report that emerin binds nuclear myosin I (NMI, a molecular motor) d

95 Furthermore, bead-conjugated emerin bound nuclear alphaII-spectrin and NMI equally we

96 NET25 rescues myogenesis after depletion of emerin but not after MAN1 silencing.

97 Overexpression of wild-type emerin, but not emerin mutant P183H (which causes EDMD a

98 hy (EMDM) patient showed complete absence of emerin by both Western blotting and immunohistochemistry

99 t epitopes on emerin in order to ensure that emerin can be distinguished from non-specific cross-reac

100 binding to emerin in vitro, predicting that emerin can form at least two distinct types of complexes

101 ms for how specific mutations in lamin A and emerin cause cardiac- or muscle-specific disease.

102 Mutations in emerin cause X-linked recessive Emery-Dreifuss muscular

103 Loss of human emerin causes Emery-Dreifuss muscular dystrophy (EDMD).

104 Loss of emerin causes Emery-Dreifuss muscular dystrophy, a tissu

105 relevant because loss or mislocalization of emerin causes Emery-Dreifuss muscular dystrophy.

106 Loss of emerin causes Emery-Dreifuss muscular dystrophy.

107 A large fragment of emerin cDNA was prepared by PCR and expressed as a recom

108 The envelope localization of Ce-lamin, Ce-emerin, Ce-MAN1, and nucleoporins are unaffected by the

109 n regions of HiLands-B and NL as measured by emerin-chromatin interaction.

110 Proposed MAN1-emerin complexes are discussed in the context of EDMD di

111 clusion chromatography yielding six distinct emerin-containing fractions (0.5-1.6 MDa).

112 n lacked ascribed functions, suggesting that emerin could have additional partners.

113 esponse to mechanical strain was impaired in emerin-deficient cells, and prolonged mechanical stimula

114 echanical stimulation increased apoptosis in emerin-deficient cells.

115 Emerin-deficient mouse embryo fibroblasts have abnormal

116 Thus, emerin-deficient mouse embryo fibroblasts have apparentl

117 tiation potential of lamin A/C-deficient and emerin-deficient myoblasts may in part underlie the dyst

118 lar strain experiments, and the integrity of emerin-deficient nuclear envelopes appeared normal in a

119 Only one complete emerin deletion has been reported previously.

120 emerin may place constraints upon potential emerin deletions and probably accounts for the rarity of

121 probably accounts for the rarity of complete emerin deletions in EMD patients.

122 tional nuclear movement and actin flow as in emerin-depleted cells.

123 ically coimmunoprecipitated with emerin, and emerin depletion prevented myosin IIB localization near

124 A polyclonal rabbit antiserum against emerin did recognize both nuclear membrane and intercala

125 e report that Lim-domain only 7 (Lmo7) binds emerin directly with 125 nM affinity; the C-terminal hal

126 ions to their nuclear envelope integrity and emerin distribution.

127 ins from HeLa cell nuclear lysates that bind emerin either directly or indirectly.

128 sed by mutations in either the X-linked gene emerin (EMD) or the autosomal lamin A/C (LMNA) gene.

129 Several mAbs against different emerin epitopes did not recognize intercalated discs in

130 Emerin expression is not, however, necessary for infecti

131 ectively, these data support a model whereby emerin facilitates repressive chromatin formation at the

132 We determined the binding affinities of emerin for GCL, BAF, and lamin A and analyzed their olig

133 We showed that emerin forms stable complexes with either lamin A plus G

134 GCL co-immunoprecipitates with emerin from HeLa cells.

135 iac defects in EDMD are caused by absence of emerin from intercalated discs.

136 rane helix caused almost complete absence of emerin from muscle with no localization to the nuclear m

137 ow--defects that are mediated by the loss of emerin from the nuclear envelope.

138 t lack the integral nuclear membrane protein emerin, from an individual with X-linked Emery--Dreifuss

139 hts the present understanding of lamin A and emerin function in regulating nuclear architecture, gene

140 Emerin function is likely to be important because, when

141 These results show that emerin functions with myosin IIB to polarize actin flow

142 The 20 kb deletion includes the entire emerin gene and extends well into most of the distal inv

143 ercalated discs were due to a product of the emerin gene and, therefore, cast some doubt upon the hyp

144 llowed us to characterize the first complete emerin gene deletion mutation that also involved a parti

145 Two key results show that Lmo7 regulates emerin gene expression: rat Lmo7 isoforms directly activ

146 EMD is caused by mutations in the 2 kb emerin gene that is located within human Xq28.

147 inds emerin protein but is also required for emerin gene transcription.

148 ovel deletion of the last three exons of the emerin gene, a carrier had a cardiomyopathy and very low

149 The emerin gene, located in human Xq28, is approximately 2 k

150 Fourteen had mutations in the X-linked emerin gene, while three showed evidence of autosomal in

151 Because emerin has been suggested to be important for infection

152 ed in Caenorhabditis elegans, but loss of Ce-emerin has no detectable phenotype.

153 Emerin has proposed roles in nuclear architecture and ge

154 Human fibroblasts that are null for emerin have an autostimulatory growth phenotype.

155 Thus, NET25 and emerin have at least partially overlapping functions dur

156 ) down-regulated for either A-type lamins or emerin have impaired differentiation potentials.

157 lamins and lamina-associated proteins, like emerin, have a regulatory role, as well as a structural

158 ation with BAF by 58% and also increased GFP-emerin hyper-phosphorylation.

159 Some emerin hyperphosphorylation can be inhibited by the prot

160 Infection causes hyperphosphorylation of emerin in a manner dependent upon both pUL34 and pUS3.

161 , we describe the derivation of mice lacking emerin in an attempt to derive a mouse model for EDMD1.

162 These results indicate a new function for emerin in cell polarization and suggest that laminopathi

163 Biochemical roles for emerin in gene expression are discussed.

164 tide libraries and has been used to localize emerin in human and rabbit heart.

165 As the expression of human emerin in mouse knockout cells fails to affect the level

166 studies indicate roles for A-type lamins and emerin in myogenic differentiation and also suggest that

167 ecognise at least four different epitopes on emerin in order to ensure that emerin can be distinguish

168 role for the inner nuclear membrane protein emerin in orienting human immunodeficiency virus type 1

169 s prompted us to reexamine the role of human emerin in supporting HIV-1 and MLV infection.

170 tantly, BAF competed with GCL for binding to emerin in vitro, predicting that emerin can form at leas

171 elated with normal or increased affinity for emerin in vitro.

172 f human Lmo7 (hLmo7C) was sufficient to bind emerin in vitro.

173 HIV-1 cDNA associated with emerin in vivo, and the interaction of viral cDNA with c

174 Moreover, following siRNA knockdown of emerin in wild-type fibroblasts, the centrosome also bec

175 Thus, disruptions in nesprin/lamin/emerin interactions might play a role in the muscle-spec

176 Emerin interacts with beta-catenin through a conserved a

177 We show that emerin interacts with tubulin, and that nocadozole-treat

178 stinct breakpoints within the 4.7 kb filamin-emerin intergenic region, suggesting that loss of filami

179 The type II inner nuclear membrane protein emerin is a component of the LINC complex that connects

180 Emerin is a nuclear membrane protein that interacts with

181 Emerin is a nuclear membrane protein which is missing or

182 Emerin is a type II inner nuclear membrane (INM) protein

183 When GFP-emerin is expressed in HEK293 cells, beta-catenin is res

184 Emerin is immediately distal to the 26 kb filamin gene,

185 The function of MAN1 is unknown, whereas emerin is known to interact with nuclear lamins, barrier

186 Immunofluorescence microscopy showed that emerin is located at the nuclear rim in all tissues exam

187 We also find that a significant fraction of emerin is located at the outer nuclear membrane and peri

188 shapen and structurally weakened nuclei, and emerin is mislocalized away from the nuclear envelope.

189 ce of emerin protein and, by extension, that emerin is not a universally important regulator of HIV-1

190 This suggests that emerin is not necessary for localizing chromosomes at th

191 antipoxviral effector, while the presence of emerin is not required.

192 However, the LEM domain protein emerin is recruited to cytoplasmic DNA in a BAF-dependen

193 Immediately centromeric to emerin is the 26-kb filamin gene (FLN1), composed of 48

194 Here we show that one function of Emerin is to regulate the flux of beta-catenin, an impor

195 y in mouse embryonic fibroblasts (MEFs) from emerin knockout, LAP2alpha knockout, or emerin and LAP2a

196 However, two other conserved regions of emerin lacked ascribed functions, suggesting that emerin

197 g to emerin and lamin A, and thereby weakens emerin-lamin interactions during both mitosis and interp

198 ocalization of nesprins and impaired nesprin/emerin/lamin binding interactions were common features o

199 nd cytoskeleton because of perturbed nesprin/emerin/lamin interactions.

200 infect primary cells from mice deficient for emerin, LAP2alpha, or both emerin and LAP2alpha.

201 s been recruited by pUL34 hyperphosphorylate emerin, leading to disruption of its connections with la

202 Disruption of NL proteins such as lamin and emerin leads to developmental defects and human diseases

203 a carrier had a cardiomyopathy and very low emerin levels (<5% of normal) due to skewed X-inactivati

204 Emerin levels in female carriers often deviated from the

205 EDMD is not caused by indirect reduction of emerin levels.

206 er-4-nonphosphorylated BAF normally promotes emerin localization at the nuclear envelope.

207 Changes in emerin localization, nuclear shape, and lamin organizati

208 -autointegration factor (BAF), the LEM (LAP, emerin, MAN) binding partner of emerin, was required for

209 BAF binds directly to LEM (LAP2, emerin, MAN1) domain nuclear membrane proteins, includin

210 eh2p-two conserved members of the LEM (Lap2, emerin, MAN1) family of integral inner nuclear membrane

211 Emerin, MAN1, and LAP2 are integral membrane proteins of

212 Emerin, MAN1, and LBR are three integral inner nuclear m

213 e then studied the diffusional mobilities of emerin, MAN1, and LBR using fluorescence recovery after

214 cleoporin ELYS, lamin B1, and four proteins (emerin, MAN1, LAP1, and LBR) of the inner nuclear membra

215 mediated by its ESCRT-II domain and the LAP2-emerin-MAN1 (LEM) family of integral inner nuclear membr

216 that Lem2p (LEM2), a member of the LEM (Lap2-Emerin-Man1) family of inner nuclear membrane proteins,

217 mediated by Heh2, a member of the LEM (Lap2-emerin-MAN1) family of integral inner nuclear membrane p

218 The loss of emerin may be the basis of nuclear morphological deforma

219 ed that loss of the nuclear envelope protein emerin may mediate the consequences of GATA6 suppression

220 nd skeletal muscle nuclei which already lack emerin may offer an alternative explanation of why these

221 Thus, the close proximity of filamin to emerin may place constraints upon potential emerin delet

222 iscovered that these "unascribed" domains of emerin mediate direct binding to a transcriptional repre

223 imetic BAF missense mutant S4E, but not S4A, emerin mislocalized from the nuclear envelope, suggestin

224 mapped to six specific sites throughout the emerin molecule using phage-displayed peptide libraries

225 ated a luciferase reporter gene in vivo, and emerin mRNA expression decreased 93% in Lmo7-downregulat

226 was due, in at least two families, to skewed emerin mRNA expression from the normal and mutated allel

227 Overexpression of wild-type emerin, but not emerin mutant P183H (which causes EDMD and selectively d

228 In contrast, expression of an emerin mutant, lacking its APC-like domain (GFP-emerinDe

229 Twelve of the 14 emerin mutations caused early termination of translation

230 ws that DNA analysis is necessary to exclude emerin mutations in suspected X-linked EDMD.

231 e model for disease pathogenesis of LMNA and emerin mutations is cell-specific perturbations of the m

232 genes in response to strain, suggesting that emerin mutations may act through altered transcriptional

233 rays), including EDMD patients with LMNA and emerin mutations.

234 odel for downstream consequences of LMNA and emerin mutations.

235 UL34 protein (pUL34) and US3 protein (pUS3), emerin no longer colocalizes with lamins, suggesting tha

236 In fibroblasts depleted of emerin, nuclei moved nondirectionally or completely fail

237 We used antibodies against Ce-MAN1, Ce-emerin, nucleoporins, and Ce-lamin to determine the timi

238 Yet emerin null mice are essentially normal, suggesting the

239 in mice also induces muscle abnormalities in emerin null mice.

240 Emerin-null cells also had significantly less HDAC3 at t

241 Emerin-null cells exhibit an epigenetic signature simila

242 mulated the catalytic activity of HDAC3, and emerin-null cells exhibit increased H4K5 acetylation, wh

243 wn to be misregulated in X-EDMD patients and emerin-null mice was confirmed by real-time PCR.

244 In emerin-null or -deficient human dermal fibroblasts we fi

245 growth is not impaired in cells derived from emerin-null transgenic mice.

246 py the detached centrosome characteristic of emerin-null/deficient cells.

247 Emerin O-GlcNAcylation was reduced ~50% by S53A or S54A

248 ced emerin production, but normal amounts of emerin of normal size were found in leucocytes and lymph

249 Inhibition by emerin of YT521-B-dependent splice site selection in viv

250 Here, we examined the function of emerin on nuclear mechanics and strain-induced signaling

251 Mutations in either emerin or lamin A/C cause Emery-Dreifuss muscular dystro

252 omorphic (LEM-2-null and heterozygous for Ce-emerin) or null for both proteins.

253 action (RT-PCR) validations in both LMNA and emerin patient muscle.

254 ter region was expected to result in reduced emerin production, but normal amounts of emerin of norma

255 to be important because, when it is mutated, emerin promotes both skeletal muscle and heart defects.

256 efficiently infects cells in the absence of emerin protein and, by extension, that emerin is not a u

257 Thus, Lmo7 not only binds emerin protein but is also required for emerin gene tran

258 e been studied both by DNA sequencing and by emerin protein expression.

259 Mouse embryo fibroblasts ablated for emerin protein through gene knockout support the same le

260 This shows that mutant emerin proteins are unstable if they are unable to integ

261 Flanking this 48-kb FLN1/emerin region are two large inverted repeats, each 11.3

262 26 kb filamin gene, and flanking the filamin-emerin region are two large inverted repeats.

263 homogeneity and inversion of the 48-kb FLN1/emerin region.

264 in many laminopathies, whereby lamin A/C and emerin regulate gene expression through modulation of nu

265 protein in all tissues tested, though minor emerin-related bands were also detected in some tissues.

266 ional repressor, GCL, and by suggesting that emerin-repressor complexes might be regulated by BAF.

267 These findings support the hypothesis that emerin scaffolds a variety of functionally distinct mult

268 Although mice lacking emerin show no overt pathology, muscle regeneration in t

269 hy, and Lmna(LCO/LCO) cells displayed normal emerin targeting and exhibited only very minimal alterat

270 ximately 40-residue LEM homology domain with emerin, the protein mutated in X-linked Emery-Dreifuss m

271 ylated BAF has a positive role in localizing emerin; this role may be disease relevant because loss o

272 isrupt nuclear localization of lamin A/C and emerin, thus linking together two common mechanisms of i

273 h sequence and structural homologies between emerin, thymopoietins and the nuclear lamina-associated

274 ese interactions, we used antibodies against emerin to affinity-purify emerin-associated protein comp

275 In mammalian cells, BAF recruits emerin to chromatin during nuclear assembly.

276 le-null animals used the maternal pool of Ce-emerin to develop to the larval L2 stage, then arrested.

277 bust to target green fluorescent protein and emerin to intranuclear sites that contained the UL31 pro

278 iral cDNA with emerin and for the ability of emerin to support virus infection.

279 amin B1 is not essential for localization of emerin to the nuclear lamina.

280 , TBLR1, and NCoR each co-immunoprecipitated emerin, validating one putative complex.

281 Infection of primary macrophages lacking emerin was abortive in that viral cDNA localized to the

282 Although emerin was abundant in the membranes of cardiomyocyte nu

283 ina" structure, or with a complex containing emerin was confirmed by GFP pull down.

284 A 'bipartite' binding site for YT521-B in emerin was identified using alanine substitution or dise

285 In the three autosomal cases of EDMD, emerin was normal on western blots of blood cells, which

286 ation of brain and liver tissues showed that emerin was present in nuclei purified by centrifugation

287 This distribution of emerin was similar to that of lamin A, a candidate gene

288 he LEM (LAP, emerin, MAN) binding partner of emerin, was required for the association of viral cDNA w

289 Using recombinant bead-conjugated emerin, we affinity-purified seven proteins from HeLa ce

290 thesis that MAN1 function might overlap with emerin, we tested different polypeptide fragments of MAN

291 wo nuclear envelope defects (EDMD LMNA, EDMD emerin) were highly related disorders and were also rela

292 -membrane-associated proteins, lamin A/C and emerin, were mislocalized throughout the nucleoplasm.

293 Therefore emerin, which bridges the interface between the inner nu

294 c expression of the nuclear envelope protein emerin, which is mislocalized in Lmna mutant cells and a

295 na-associated protein, LAP2, we suggest that emerin will prove to be one member of a family of inner

296 pes were reproduced by direct suppression of emerin with siRNA.

297 only lamin-A can ensure the localization of emerin within the NL.