ライフサイエンスコーパス: LEDGF

1 LEDGF associates with mixed-lineage leukemia (MLL) fusio

2 LEDGF binding to IN dimers had a k(on) of 0.0285 nm(-1).

3 LEDGF dominant interference and depletion impair HIV-1 i

4 LEDGF is thus the first example of a cellular protein co

5 LEDGF modestly stimulated (two- to threefold) concerted

6 LEDGF mRNA and protein levels and mRNA levels of known s

7 LEDGF normally directs integrations to the bodies of exp

8 LEDGF potently stimulated strand transfer activity of di

9 LEDGF PWWP exhibits nanomolar binding affinity to purifi

10 LEDGF strongly stabilized these interactions and promote

11 LEDGF tethers IN to the host chromatin and enables targe

12 LEDGF/p75 and HRP2 are predicted to share a similar doma

13 LEDGF/p75 and HRP2 IBDs avidly bound HIV-1 IN in an in v

14 LEDGF/p75 dependence is universally conserved in the ret

15 LEDGF/p75 depletion by contrast preferentially altered p

16 LEDGF/p75 directly interacts with lentiviral integrase p

17 LEDGF/p75 interactions with lentiviral integrases are we

18 LEDGF/p75 is also able to act as a molecular tether link

19 LEDGF/p75 is known to enhance the integrase strand trans

20 LEDGF/p75 was not displaced from IN during aggregation,

21 LEDGF/p75, a chromatin reader recognizing H3K36me3 marks

22 LEDGF/p75, a key cellular binding partner of the lentivi

23 LEDGF/p75, which promotes viral integration into active

24 Functional characterizations demonstrate a LEDGF/p75-independent role of SSRP1 in the regulation of

25 nterface inhibits IN enzymatic activity in a LEDGF-independent manner.

26 stigate in vivo chromatin binding of JPO2, a LEDGF/p75- and c-Myc-interacting protein involved in tra

27 electively impaired upon overexpression of a LEDGF/p75-binding cyclic peptide CP65, originally develo

28 epletion of the transcriptional co-activator LEDGF/p75 by RNA interference alters the genome-wide pat

29 Transcriptional co-activator LEDGF/p75 is the major cellular interactor of HIV-1 inte

30 ce spectroscopy, we identified an additional LEDGF/p75-MLL interface, which overlaps with the binding

31 t for enzymatic activities and high affinity LEDGF binding.

32 came functional with a delay of 45 min after LEDGF/p75 addition.

33 entified through competition binding against LEDGF.

34 for the development of therapeutics against LEDGF/p75-dependent MLL fusion-driven leukemic disorders

35 cleases (TALENs) to completely eradicate all LEDGF/p75 expression.

36 g chromatin locking is not a property of all LEDGF/p75-binding proteins.

37 nds impairs both integrase-LEDGF binding and LEDGF-independent integrase catalytic activities with si

38 from both the PHD finger fusion-directed and LEDGF-directed integration sites.

39 the importance of the order of viral DNA and LEDGF/p75 addition to IN for productive concerted integr

40 o tetramers in the presence of viral DNA and LEDGF/p75.

41 ctor implicated in viral nuclear import) and LEDGF/p75 in the targeting of the viral preintegration c

42 the interactions between full-length IN and LEDGF.

43 iffusive JPO2 can oligomerize; that JPO2 and LEDGF/p75 interact directly and specifically in vivo thr

44 veral studies have shown that both MENIN and LEDGF/p75 are required for efficient MLL-fusion-mediated

45 e assembly and the main ALLINI mechanism are LEDGF/p75 independent.

46 racting protein 1 (PSIP1)/p75, also known as LEDGF, whose PWWP domain binds to H3K36me3, interacts wi

47 sistent with a role for chromatin-associated LEDGF/p75 in stimulating integrase activity during infec

48 e affinities between IN monomers and between LEDGF and IN dimers.

49 ase dimerization and the interaction between LEDGF and IN dimers.

50 Mechanistically, the chromatin-bound LEDGF, through its interaction with KAT5, promoted chrom

51 nd was found to bind at the site occupied by LEDGF/p75 on IN by x-ray crystallography.

52 ts, (ii) less frequent in genes regulated by LEDGF/p75 and (iii) more frequent in GC-rich DNA.

53 ntiviral PIC nuclear import is unaffected by LEDGF/p75 knockdown, this protein is a component of func

54 unaffected by total eradication of cellular LEDGF/p75.

55 We demonstrate that cellular LEDGF/p75 is tightly bound to mononucleosomes (MNs).

56 Chronic LEDGF treatment via AAV-Ledgf administration gave succes

57 d instead by the transcriptional coactivator LEDGF/p75, which was required for nuclear localization.

58 with viral DNA and its key cellular cofactor LEDGF to effectively integrate the reverse transcript in

59 for binding to its cognate cellular cofactor LEDGF/p75 during early steps of HIV-1 infection.

60 it IN interaction with its cellular cofactor LEDGF/p75 with comparable potencies in vitro, their prim

61 f integrase-to-chromatin-tethering-competent LEDGF/p75.

62 c cells expressing MLL interaction-defective LEDGF/p75 mutants revealed that this interaction is esse

63 rfering RNA expression eliminated detectable LEDGF/p75 expression and caused dramatic, stable redistr

64 f intact IN tetramers bound to two different LEDGF truncations allow for placement of the integrase b

65 ely restored by ectopic expression of either LEDGF/p75 or HRP2.

66 tion complexes (PICs) showed that endogenous LEDGF/p75 is a component of functional HIV-1 and FIV PIC

67 es, we used TALENs to definitively eradicate LEDGF/p75 by deleting either all of PSIP1 or the exons t

68 The host chromatin-binding factor LEDGF/p75 interacts with HIV-1 integrase and directs int

69 otein Lens Epithelium-Derived Growth Factor (LEDGF) and human immunodeficiency virus (HIV) integrase

70 h the lens epithelium-derived growth factor (LEDGF) binding pocket on IN and were identified through

71 r p75/lens epithelium-derived growth factor (LEDGF) binds human immunodeficiency virus type 1 (HIV-1)

72 actor lens epithelium-derived growth factor (LEDGF) by menin indicates that menin is a molecular adap

73 Lens epithelium-derived growth factor (LEDGF) fusion proteins can direct HIV-1 DNA integration

74 Lens epithelium-derived growth factor (LEDGF) is a chromatin-associated protein implicated in l

75 Lens epithelium-derived growth factor (LEDGF) is upregulated in response to stress and enhances

76 Lens epithelium-derived growth factor (LEDGF) proteins p75 and p52 are transcriptional coactiva

77 Lens epithelium derived growth factor (LEDGF), a nuclear protein, plays a role in regulating th

78 to as lens epithelium-derived growth factor (LEDGF), is the dominant cellular binding partner of HIV-

79 vator lens epithelium-derived growth factor (LEDGF)/p75 (p75) is an essential HIV integration cofacto

80 PSIP1/lens epithelium-derived growth factor (LEDGF)/p75 are available, many questions remain regardin

81 cipal lens epithelium-derived growth factor (LEDGF)/p75 binding pocket.

82 th IN-lens epithelium-derived growth factor (LEDGF)/p75 binding.

83 Lens epithelium-derived growth factor (LEDGF)/p75 functions as a bimodal tether during lentivir

84 N) to lens epithelium-derived growth factor (LEDGF)/p75 in large part determines the efficiency and s

85 Lens epithelium-derived growth factor (LEDGF)/p75 is a cellular cofactor for HIV-1 DNA integrat

86 Human lens epithelium-derived growth factor (LEDGF)/p75 protein forms a specific nuclear complex with

87 otein lens epithelium-derived growth factor (LEDGF)/p75 underlies the targeting of gene bodies, where

88 e and lens epithelium-derived growth factor (LEDGF)/p75.

89 actor lens epithelium-derived growth factor (LEDGF)/p75.

90 otein lens epithelium-derived growth factor (LEDGF)/transcriptional coactivator p75 are an emerging c

91 h the lens epithelium-derived growth factor (LEDGF/p75) and MENIN.

92 lular lens epithelium-derived growth factor (LEDGF/p75) binds both chromosomal DNA and HIV integrase,

93 Lens epithelium-derived growth factor (LEDGF/p75) is a transcriptional co-activator involved in

94 Lens epithelium-derived growth factor (LEDGF/p75) tethers lentiviral preintegration complexes (

95 The lens epithelium-derived growth factor (LEDGF/p75), an IN interacting cellular cofactor, has bee

96 with lens epithelium-derived growth factor (LEDGF/p75; encoded by the PSIP1 gene) and MENIN.

97 uided by integrase-interacting host factors (LEDGF/p75 for HIV-1 and BET proteins for MoMLV) that tet

98 iviral INs possessed detectable affinity for LEDGF in either pull-down or yeast two-hybrid assays.

99 ced a K(i) value of 35 nm when competing for LEDGF binding to IN dimers.

100 alyzed HIV integration in cells depleted for LEDGF/p75, and found that integration was (i) less frequ

101 persists in Psip1 (the gene that encodes for LEDGF/p75) knockout (KO) cells.

102 nd IN-binding domains that are important for LEDGF/p75 co-factor function.

103 N by ALLINIs together with the inability for LEDGF/p75 to effectively engage the virus during its egr

104 results establish a molecular mechanism for LEDGF/p75-mediated tethering of HIV-1 integrase to chrom

105 ents in these cells also excluded a role for LEDGF/p75 in HIV-1 assembly and showed that the main ALL

106 In the same format, LEDGF produced a K(i) value of 35 nm when competing for

107 racterized, but the structural basis for how LEDGF/p75 engages chromatin is unknown.

108 These findings provide new insight into how LEDGF modulates HIV-1 IN structure and function, and hig

109 To understand how LEDGF/p75 recognizes transcription units, we sequenced 1

110 Previously identified LEDGF hotspot residues anchor the protein to both monome

111 Mutation of Asp-366 to Asn in LEDGF ablated the interaction, suggesting a common mecha

112 that HIV-1 IN is exclusively cytoplasmic in LEDGF/p75-deficient cells, but mainly nuclear in LEDGF/p

113 ynamics requires a functional PWWP domain in LEDGF/p75.

114 F/p75-deficient cells, but mainly nuclear in LEDGF/p75 wild type cells, and that cytoplasmic HIV-1 IN

115 Virions produced in LEDGF/p75-deficient cells had normal infectivity.

116 ignificantly enriched, relative to random in LEDGF/p75 deficient cells, other host factors likely con

117 ene expression were significantly reduced in LEDGF-null cells.

118 is that evolutionarily conserved regions in LEDGF/p75 exposed to solvent and harboring posttranslati

119 , HIV-1 and FIV infection and replication in LEDGF/p75-deficient cells was equivalent to that in cont

120 ncreasing IN protein levels to those seen in LEDGF/p75 wild type cells and implicating proteasomal de

121 1 IN protein was found to be much shorter in LEDGF/p75-deficient cells.

122 The IN-viral DNA and IN-LEDGF/p75 complexes yielded significantly different FRET

123 inor effect on the ALLINI IC50 values for IN-LEDGF/p75 binding.

124 otein-protein contacts in the full-length IN-LEDGF complex that lay outside of the observable IBD-CCD

125 f IN-viral DNA assembly and inhibition of IN-LEDGF interaction.

126 ily target IN multimerization rather than IN-LEDGF/p75 binding.

127 nt of the subcellular localization of the IN-LEDGF complex.

128 ture of the IN-IN dimer compared with the IN-LEDGF interaction.

129 iral DNA yielded FRET very similar to the IN-LEDGF/p75 complex.

130 ing between ALLINI and IN that mimics the IN-LEDGF/p75 interaction but instead altered the positionin

131 romolar IC50 values for inhibition of the IN-LEDGF/p75 interaction, but significant cytotoxicity was

132 ssociated functions, IN catalysis and the IN-LEDGF/p75 interaction, determines the multimode mechanis

133 roxyquinolines as novel inhibitors of the IN-LEDGF/p75 interaction.

134 and extend existing biochemical data for IN.LEDGF complexes and lend new insights into the quaternar

135 e, stoichiometry, and molecular shapes of IN.LEDGF complexes in solution.

136 In addition, these compounds inhibit LEDGF binding to the stable synaptic complex.

137 al mechanism of LEDGINs is that they inhibit LEDGF binding to IN, which prevents targeted integration

138 The most active derivative (5) inhibited LEDGF/p75-dependent HIV-1 IN activity in vitro with an I

139 ed SUMO acceptor sites drastically inhibited LEDGF SUMOylation, extended the half-life of LEDGF/p75,

140 is class of compounds impairs both integrase-LEDGF binding and LEDGF-independent integrase catalytic

141 eported to selectively inhibit the integrase-LEDGF interaction in vitro and impair HIV-1 replication

142 transcribed euchromatin, where the integrase-LEDGF/p75 interaction drives integration into gene bodie

143 The molecular basis for the integrase-LEDGF/p75 interaction is understood, while the mechanism

144 into active genes, reducing integration into LEDGF/p75-regulated genes, and increasing integration in

145 levels of IN protein than introduction into LEDGF/p75 wild type cells.

146 c feed-forward regulatory circuits involving LEDGF/p75 and AKT that promote metastatic phenotypes in

147 and showed that the main ALLINI mechanism is LEDGF/p75 independent.

148 oci in medulloblastoma and point to the JPO2:LEDGF/p75 protein complex as a potentially new targetabl

149 hich overlaps with the binding site of known LEDGF/p75 interactors-HIV-1 integrase, PogZ, and JPO2.

150 this correlation was absent in cells lacking LEDGF.

151 (RNA-seq) analysis of HEK293T cells lacking LEDGF/p75 or the LEDGF/p75 integrase-binding domain (IBD

152 PWWP or the AT-hook domain from full-length LEDGF/p75 reduced Triton-resistant chromatin binding, wh

153 Biochemical analysis showed that full-length LEDGF/p75 resists Triton X-100 extraction from chromatin

154 Genome-wide studies have located LEDGF/p75 inside actively transcribed genes where it med

155 These data corroborate the MLL-LEDGF/p75 interaction as novel target for the treatment

156 exes with MLL1 or with JUND, or with an MLL1-LEDGF heterodimer.

157 ysis of the strand transfer step when 150 nM LEDGF/p75 was present during the 3'-processing step.

158 ses indicate that, in the presence of 150 nM LEDGF/p75, active integrase/donor DNA complexes were inc

159 Ala was sufficient to impair the ability of LEDGF/p75 to mediate HIV-1 DNA integration, although the

160 to integration specificity in the absence of LEDGF/p75 and HRP2.

161 integrase/donor DNA formed in the absence of LEDGF/p75 became refractory to the stimulatory effect of

162 analyze HIV-1 integration in the absence of LEDGF/p75 protein.

163 In the absence of LEDGF/p75, JPO2 performs chromatin scanning inherent to

164 re equivalent in the presence and absence of LEDGF/p75.

165 267 to 281 reduced the cofactor activity of LEDGF/p75 to levels observed for chromatin-binding-defec

166 MOylation on the transcriptional activity of LEDGF/p75.

167 otein interaction to the overall affinity of LEDGF/p75 for human chromatin.

168 nts of IN dimers (K(dimer) = 67.8 pm) and of LEDGF from IN dimers (K(d) = 10.9 nm).

169 strate for the first time the association of LEDGF proteins with the FACT complex and give further su

170 established that the simultaneous binding of LEDGF/p75 to chromatin and to HIV-1 integrase is require

171 tegrase-to-chromatin-tethering capability of LEDGF/p75.

172 tant to disruption by high concentrations of LEDGF.

173 utic target because, like CCR5, depletion of LEDGF/p75 is tolerated well by human CD4+ T cells, and k

174 dent manner that requires the PWWP domain of LEDGF proteins and the HMG domain of SSRP1.

175 The isolated IN binding domain of LEDGF was sufficient to stimulate and inhibit concerted

176 V-1 IN complexed to the IN-binding domain of LEDGF.

177 domain of JPO2 and the C-terminal domain of LEDGF/p75, comprising the integrase-binding domain; and

178 ted to a 96-well plate format, the effect of LEDGF/p75 on both the 3'-processing and strand transfer

179 came refractory to the stimulatory effect of LEDGF/p75.

180 We studied the effects of LEDGF on the assembly and activity of HIV-1 synaptic com

181 etic compartment and examined the effects of LEDGF/p75 depletion in postnatal hematopoiesis and the i

182 entified in the C-terminal part exclusive of LEDGF/p75.

183 identify the specific structural features of LEDGF involved in gene transcription.

184 this complex, understanding the function of LEDGF/p75 in normal hematopoiesis is crucial.

185 complex with the IN binding domain (IBD) of LEDGF has furthermore revealed essential protein-protein

186 ion of the integrase binding domain (IBD) of LEDGF/p75 (LEDGF) inhibits HIV-1 replication.

187 We now studied nuclear import of LEDGF/p75 in live and semipermeabilized cells.

188 We show that nuclear import of LEDGF/p75 is GTP-, Ran-, importin-alpha/beta-, and energ

189 ding to LEDGF/p75, whereas pre-incubation of LEDGF/p75 and IN followed by addition of viral DNA yield

190 Detailed analysis of the interaction of LEDGF/p75 with the FACT complex indicates that LEDGF/p75

191 reveal two distinct functional interfaces of LEDGF PWWP: a well-defined hydrophobic cavity, which sel

192 us production is independent of the level of LEDGF/p75 expression.

193 LEDGF SUMOylation, extended the half-life of LEDGF/p75, and significantly increased its transcription

194 did not affect the cellular localization of LEDGF proteins and was not necessary for their chromatin

195 control retinas to explore the mechanism of LEDGF protection.

196 However, the exact molecular mechanism of LEDGF/p75 in HIV-1 integration is not yet completely und

197 approaches, we determined the mechanisms of LEDGF/p75 DNA-binding in vitro and chromatin-association

198 We identified the NLS of LEDGF/p75 through deletion analysis and site-directed mu

199 Therefore, a panel of LEDGF/p75 deletion mutants targeting these protein regio

200 ogZ, another cellular interaction partner of LEDGF/p75.

201 manner to the trans-activation potential of LEDGF.

202 reaction remained active in the presence of LEDGF/p75, but displayed 3- to 7-fold higher IC50 values

203 gration was inhibited if the molar ratios of LEDGF to IN were >1, apparently due to the disruption of

204 Moreover, restoration of LEDGF/p75 to knocked down clones rescued HIV-1 IN stabil

205 egration is clearly established, the role of LEDGF/p75-associated proteins in HIV-1 infection remains

206 n (GFP) with multiple C-terminal segments of LEDGF inhibited HIV-1 replication substantially, but min

207 We determined the solution structure of LEDGF PWWP and monitored binding to the histone H3 tail

208 ew insights into the quaternary structure of LEDGF-bound IN tetramers.

209 n regarding the properties and structures of LEDGF-bound IN oligomers.

210 ractions as the primary antiviral targets of LEDGF/p75-binding site IN inhibitors.

211 The C terminus of LEDGF contains an integrase binding domain (IBD), and th

212 Replacing the N terminus of LEDGF with chromatin binding domains (CBDs) from other p

213 g cell nuclei was also equivalent to that of LEDGF/p75 wild-type cells.

214 N during aggregation, indicating trapping of LEDGF/p75 in aggregates.

215 nificantly reduce the dependency of HIV-1 on LEDGF/p75 during infection and that this difference corr

216 in in determining the dependency of HIV-1 on LEDGF/p75 during infection highlights a connection betwe

217 nisms of retroviral integration, focusing on LEDGF/p75--the first cellular protein shown to have a ro

218 Studies on LEDGF/p75 indicate that it directs HIV integration site

219 whereas donor DNA can engage either free or LEDGF/p75-bound integrase.

220 wth factor/transcriptional co-activator p75 (LEDGF) and human immunodeficiency virus type 1 (HIV-1) i

221 wth factor/transcriptional co-activator p75 (LEDGF/p75) protein was recently identified as a binding

222 e lens epithelium-derived growth factor p75 (LEDGF/p75) is a chromatin-bound protein essential for ef

223 Lens epithelium-derived growth factor p75 (LEDGF/p75) is a DNA-binding, transcriptional co-activato

224 N-lens epithelium-derived growth factor/p75 (LEDGF/p75) interface , we developed a set of modified 8-

225 integrase binding domain (IBD) of LEDGF/p75 (LEDGF) inhibits HIV-1 replication.

226 264 promoted aggregation of IN and preformed LEDGF/p75-IN complexes, suggesting a mechanism of inhibi

227 racting with the chromatin-anchoring protein LEDGF at a distinct surface formed by both menin and MLL

228 protein JPO2 and its partner binding protein LEDGF/p75 as critical modulators of PI3K/AKT signaling a

229 HIV-1 utilizes the cellular protein LEDGF/p75 as a chromosome docking and integration cofact

230 rough the recruitment of a cellular protein, LEDGF/p75.

231 x expression and may also explain why PSIP1 (LEDGF) is found as a fusion partner with NUP98 in myeloi

232 Here, we identified PSIP1/LEDGF (isoform p75) as a novel strong candidate gene inv

233 Our results reveal LEDGF/p75 as a critical targeting factor, commandeering

234 The same LEDGF/p75-dependent disparity was observed for feline im

235 nscription units into cells made stringently LEDGF/p75-deficient by RNAi resulted in much lower stead

236 rference (RNAi) has been useful for studying LEDGF/p75, but the potent cofactor activity of small pro

237 attractive approach to simultaneously target LEDGF in leukemia and HIV.

238 the gene activation potential of C-terminal LEDGF (aa 199-530); thus the N-terminal domain (aa 5-62)

239 C-terminal LEDGF contains activation domains, an extensive loop-reg

240 Interestingly, removal of N-terminal LEDGF (aa 1-187) significantly enhances the gene activat

241 sclosed the DNA-binding domain of N-terminal LEDGF mapped between amino acid residues 5 and 62, a 58

242 that CPSF6 played a more dominant role than LEDGF/p75 in directing integration to euchromatin.

243 We conclude that LEDGF/p75 fully accounts for cellular trafficking of div

244 Collectively, our results demonstrate that LEDGF contains three DNA-binding domains, which regulate

245 ein interaction assays, we demonstrated that LEDGF/p75 complexes with a chromatin-remodeling complex

246 ever, compelling evidence was not found that LEDGF protection was associated with upregulation of hea

247 DGF/p75 with the FACT complex indicates that LEDGF/p75 interacts with SSRP1 in an hSpt16-independent

248 A previous study revealed that LEDGF/p75 dynamically scans the chromatin, and upon inte

249 Our data show that LEDGF differentially affects IN-DNA complexes mediating

250 Furthermore, we show that LEDGF PWWP preferentially and tightly binds to in vitro

251 5 integrase-binding domain (IBD) showed that LEDGF/p75 contributes to splicing patterns in half of th

252 Affinity purification showed that LEDGF/p75 is associated with a number of splicing factor

253 in vitro and in vivo experiments showed that LEDGF/p75 is dispensable for steady-state hematopoiesis

254 The results suggest that LEDGF may influence HIV-1 integration in vivo.

255 Some recent studies have suggested that LEDGF/p75 may participate in HIV-1 assembly.

256 The LEDGF/p75 gene, PSIP1, is a potential therapeutic target

257 The LEDGF/p75 integrase-binding domain has been established

258 The LEDGF/p75 NLS, 148GRKRKAEKQ156, belongs to the canonical

259 to perturbations of the structure around the LEDGF-binding site, we propose that small molecule inhib

260 cy of an allosteric inhibitor that binds the LEDGF/p75 binding site on IN, a result that was not sign

261 nal units occurred in genes regulated by the LEDGF/p75 transcriptional coactivator.

262 ntegration targeting, which is guided by the LEDGF/p75-IN interaction.

263 re constructed to constitutively express the LEDGF-binding VH and these cells showed interference wit

264 Here we identify a second function for the LEDGF/p75-integrase interaction.

265 ased ubiquitinated HIV-1 IN was found in the LEDGF/p75 knock-down cells.

266 de CP65, originally developed to inhibit the LEDGF/p75-HIV-1 integrase interaction.

267 plain the apparent lentiviral tropism of the LEDGF-IN interaction.

268 The crystal structure of the LEDGF-VH complex reveals that the single domain antibody

269 structural similarities, 24 residues of the LEDGF/p75 PWWP domain were mutagenized to garner essenti

270 Our results suggest that the dynamics of the LEDGF/p75-chromatin interaction depend on the specific p

271 ta represent only a partial structure of the LEDGF/p75-MLL-MENIN complex.

272 is of HEK293T cells lacking LEDGF/p75 or the LEDGF/p75 integrase-binding domain (IBD) showed that LED

273 t this domain is involved in stabilizing the LEDGF-DNA binding complex.

274 fusion protein nuclear, confirming that the LEDGF/p75 NLS is transferable.

275 which the ING2 PHD finger was linked to the LEDGF IBD directed integrations near the start sites of

276 the HP1alpha chromodomain was linked to the LEDGF IBD directed integrations to sites that differed f

277 stand the molecular mechanism underlying the LEDGF integrase-binding domain (IBD) interaction with ML

278 Among these, LEDGF has been identified as a cellular cofactor critica

279 Instead, this LEDGF/p75 added at the start of the strand transfer step

280 Thus, LEDGF/p75 interacts with splicing factors, contributes t

281 ned unchanged upon its subsequent binding to LEDGF/p75, whereas pre-incubation of LEDGF/p75 and IN fo

282 te a single VH antibody domain that binds to LEDGF.

283 ch to the chromosome when integrase binds to LEDGF/p75.

284 cs the effect of binding of HIV integrase to LEDGF which is crucial for HIV propagation.

285 Binding of these proteins or MLL to LEDGF/p75 is mutually exclusive.

286 egrase binding domain (IBD) is not unique to LEDGF/p75, as a second human protein, hepatoma-derived g

287 exon with a single TALEN pair yielded trace LEDGF/p75 levels that were virologically active, affirmi

288 We used LEDGF dominant interference to address the latter questi

289 However, using LEDGF proteins defective for nuclear localization and IN

290 -derived growth factor p75 splicing variant (LEDGF), which is a reader protein of H3K36me3, and the K

291 In contrast, when LEDGF/p75 was added at the beginning of the strand trans

292 We propose a model whereby LEDGF/p75 can only bind integrase before the latter bind

293 At present, it is not known whether LEDGF/p75-mediated chromatin locking is typical for inte

294 Combining GFP-IBD expression with LEDGF depletion was profoundly antiviral.

295 HIV-1 mutant viruses unable to interact with LEDGF indicate that IN function is highly sensitive to p

296 anemia virus (EIAV) readily interacted with LEDGF.

297 se results confirm that the interaction with LEDGF is conserved within and limited to Lentivirus and

298 Protection requires only interaction with LEDGF/p75, and it is independent of the subcellular loca

299 inding are decelerated upon interaction with LEDGF/p75, very strong locking of their complex onto chr

300 cked out CPSF6 in parallel or in tandem with LEDGF/p75.