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 The lens epithelium-derived growth factor (LEDGF) is a cellular factor that binds IN and tethers pr

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

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

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

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

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

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

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

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

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

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

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

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

87 actor lens epithelium-derived growth factor (LEDGF)/p75 that helps to guide integration into host gen

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

149 this correlation was absent in cells lacking LEDGF.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

164 267 to 281 reduced the cofactor activity of LEDGF/p75 to levels observed for chromatin-binding-defec

165 MOylation on the transcriptional activity of LEDGF/p75.

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

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

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

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

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

171 tant to disruption by high concentrations of LEDGF.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

193 control retinas to explore the mechanism of LEDGF protection.

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

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

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

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

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

199 manner to the trans-activation potential of LEDGF.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

222 c lens-epithelium-derived-growth-factor-p75 (LEDGF/p75)-binding site on HIV-1 integrase, an attractiv

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

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

225 264 promoted aggregation of IN and preformed LEDGF/p75-IN complexes, suggesting a mechanism of inhibi

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

249 5 integrase-binding domain (IBD) showed that LEDGF/p75 contributes to splicing patterns in half of th

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

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

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

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

254 The LEDGF also stimulates HIV-1 IN DNA strand transfer activ

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

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

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

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

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

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

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

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

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

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

265 peptide spanning residues 178 to 197 of the LEDGF that encompasses its AT-hook DNA-binding elements.

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

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

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

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

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

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

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

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

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

275 hibitors of HIV-1 integrase that bind to the LEDGF/p75 interaction site and disrupt the structure of

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

277 Small molecules that bind within the LEDGF/p75-binding site promote aberrant multimerization

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 sical properties of intasomes assembled with LEDGF peptide fusion IN have enabled us to determine the

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

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

297 anemia virus (EIAV) readily interacted with LEDGF.

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

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

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

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