ライフサイエンスコーパス: LANA

1 LANA achieves this by controlling its expression through

2 LANA also drives dysregulated cell growth through a mult

3 LANA also induces chromosomal instability, thus promotin

4 LANA also simultaneously binds to TR DNA and mitotic chr

5 LANA binds cooperatively to the terminal repeat (TR) reg

6 LANA binds the KSHV terminal-repeat (TR) sequence throug

7 LANA binds the KSHV terminal-repeat (TR) sequence to med

8 LANA binds to KSHV terminal repeat (TR) DNA and tethers

9 LANA bound with high occupancy to the KSHV genome termin

10 LANA has also been suggested to affect host gene express

11 LANA interacts with the components of multiple cellular

12 LANA is known to activate ERK and limit the activity of

13 LANA is required for tethering of the KSHV episome to th

14 LANA mediates KSHV DNA replication and segregates episom

15 LANA recruited PCNA to the KSHV genome via Bub1 to initi

16 LANA recruitment sites on the KSHV genome inversely corr

17 LANA self-associates to bind KSHV terminal-repeat (TR) D

18 LANA simultaneously binds mitotic chromosomes and TR DNA

19 LANA with point mutations in the carboxyl-terminal domai

20 LANA with this downstream sequence deleted maintained th

21 LANA-associated TIP60 retained acetyltransferase activit

22 h KSHV latency-associated nuclear antigen 1 (LANA-1) and the host transcriptional repressor KAP1, whi

23 g only latency-associated nuclear antigen 1 (LANA-1) protein, and in KSHV latently infected primary e

24 e KSHV latency-associated nuclear antigen 1 (LANA-1; ORF73) and LANA-1 nuclear puncta.

25 Seropositivity, defined by K8.1/LANA or in combination with 5 other KSHV antigens (ORF59

26 We show that KSHV LANA and MHV-68 LANA proteins bind LBS DNA using strikingly different mo

27 n-incompetent adenovirus type 5 to deliver a LANA-specific Cas9 system (Ad-CC9-LANA) into various KSH

28 iched at the KSHV TR during S phase and in a LANA-dependent manner.

29 Therefore, this work identifies adjacent LANA regions with distinct roles in episome segregation

30 In summary, this work identifies adjacent LANA sequence with distinct roles in episome segregation

31 TR) region of the viral episome via adjacent LANA binding sites (LBS), but the molecular mechanism by

32 ions is a regulated phenomenon, which allows LANA to interact with cellular components in different c

33 Our data further support a role for Bub1 and LANA in PCNA-mediated cellular DNA replication processes

34 roteins for replication and maintenance, and LANA has been shown to make many of these proteins avail

35 he classic histological features of MCD, and LANA-1 immunostaining identified HHV-8-infected plasmabl

36 ciated nuclear antigen 1 (LANA-1; ORF73) and LANA-1 nuclear puncta.

37 nteractions between ANG-LANA-1, ANG-p53, and LANA-1-p53, the induction of p53, p21, and Bax proteins,

38 latent proteins, including vIRF3, vFLIP, and LANA, target the expression, function, and stability of

39 G levels, decreased interactions between ANG-LANA-1, ANG-p53, and LANA-1-p53, the induction of p53, p

40 -encoded latency-associated nuclear antigen (LANA) disrupts the association of CIITA with the MHC-II

41 of KSHV latency-associated nuclear antigen (LANA) dots, as detected by immunofluorescence microscopy

42 The latency-associated nuclear antigen (LANA) encoded by KSHV plays a key role in regulating a n

43 with the latency-associated nuclear antigen (LANA) encoded by KSHV.

44 s (KSHV) latency-associated nuclear antigen (LANA) is a 1,162-amino-acid protein that mediates episom

45 s (KSHV) latency-associated nuclear antigen (LANA) is a 1,162-amino-acid protein that mediates the ma

46 Latency-associated nuclear antigen (LANA) is a conserved gamma-2-herpesvirus protein importa

47 Latency-associated nuclear antigen (LANA) is a conserved Rhadinovirus protein that is necess

48 Latency-associated nuclear antigen (LANA) is a conserved, multifunctional protein encoded by

49 Latency-associated nuclear antigen (LANA) is a multifunctional protein encoded by members of

50 cts, the latency-associated nuclear antigen (LANA) is absolutely required in the maintenance, replica

51 Latency-associated nuclear antigen (LANA) is central to episomal tethering, replication and

52 Latency-associated nuclear antigen (LANA) is essential for maintaining the viral genome by r

53 Latency-associated nuclear antigen (LANA) is one of the major proteins expressed during late

54 The latency-associated nuclear antigen (LANA) is required for latent replication and persistence

55 Latency-associated nuclear antigen (LANA) is the most abundantly expressed protein during la

56 KSHV latency-associated nuclear antigen (LANA) mediates persistence of viral episomes in latently

57 The latency-associated nuclear antigen (LANA) of Kaposi sarcoma herpesvirus (KSHV) is mainly loc

58 The latency-associated nuclear antigen (LANA) of the Kaposi's sarcoma-associated herpesvirus (KS

59 xpressed latency-associated nuclear antigen (LANA) of the virus.

60 -encoded latency-associated nuclear antigen (LANA) protein functions in latently infected cells as an

61 rescence labeling of latent nuclear antigen (LANA) protein, together with fluorescence in situ RNA hy

62 -encoded latency-associated nuclear antigen (LANA) to repress expression of the major lytic replicati

63 pesvirus latency-associated nuclear antigen (LANA)(1-23), human papillomavirus 8 E2, and prototype fo

64 Latency-associated nuclear antigen (LANA), a multifunctional protein expressed by the Kaposi

65 Latency-associated nuclear antigen (LANA), the most abundantly expressed protein, is essenti

66 osome by latency associated nuclear antigen (LANA), which binds in the terminal repeat (TR) region of

67 ding the latency-associated nuclear antigen (LANA), which mediates viral episome persistence.

68 CMs, and latency-associated nuclear antigen (LANA).

69 th viral latency-associated nuclear antigen (LANA).

70 pesvirus latency-associated nuclear antigen (LANA).

71 sing its latency-associated nuclear antigen (LANA).

72 abundant latency-associated nuclear antigen, LANA, on the host genome and its impact on host gene exp

73 proteins with intrinsic properties, such as LANA, that minimize epitope recognition by CD8(+)T cells

74 ficantly reduced in KSHV-infected as well as LANA-expressing B cells.

75 es as a scaffold or molecular bridge between LANA and PCNA.

76 es as a scaffold or molecular bridge between LANA and PCNA.

77 ub1 are required for the interaction between LANA and Bub1.

78 hat are required for the interaction between LANA and Bub1.

79 d a cell cycle-dependent interaction between LANA and MCMs and determined their importance for viral

80 Therefore, the interaction between LANA and RLIM could be detected in coimmunoprecipitation

81 ral drugs to inhibit the interaction between LANA and the viral genome.

82 dy, we characterize the interactions between LANA and minichromosome maintenance (MCM) proteins, memb

83 icant reductions in the KSHV episome burden, LANA RNA and protein expression over time, but this effe

84 n effect that is exploited during latency by LANA-1-mediated recruitment of the host transcriptional

85 The downregulation of Bub1 mediated by LANA resulted in chromosomal instability, a hallmark of

86 egulation by RLIM substrates is modulated by LANA.

87 egulated in latent infection are occupied by LANA at their promoters.

88 erstand the conserved functions performed by LANA homologs, we generated a recombinant MHV68 virus th

89 tein-Barr virus, specific DNA recognition by LANA is highly asymmetric.

90 and endothelial cells transduced with Ad-CC9-LANA underwent significant reductions in the KSHV episom

91 deliver a LANA-specific Cas9 system (Ad-CC9-LANA) into various KSHV latent target cells.

92 By directly binding to cGAS, LANA, and particularly, a cytoplasmic isoform, inhibit t

93 In contrast, LANA rapidly disassociates from episomes during reactiva

94 ized by high-level expression of cytoplasmic LANA and nuclear ORF59, a marker of lytic replication.

95 We confirmed the presence of cytoplasmic LANA in a subset of cells in lytically active multicentr

96 cellular interaction partner of cytoplasmic LANA isoforms.

97 metry analysis demonstrated that cytoplasmic LANA isoforms were full length, containing the N-termina

98 arities in their DNA-binding domains (DBDs), LANA homologs from Kaposi sarcoma-associated herpesvirus

99 nuclear translocation resulted in decreased LANA-1 gene expression and reduced KSHV-infected endothe

100 We also detected LANA along with MCMs at the replication forks using a no

101 This suggests that direct LANA binding to promoters is not the prime determinant o

102 lex with its high-affinity viral target DNA, LANA binding site 1 (LBS1), at 2.9 A resolution.

103 arcoma-associated herpesvirus (KSHV)-encoded LANA protein enhances the ubiquitin ligase activity of R

104 The KSHV-encoded LANA protein is multifunctional and promotes both cell g

105 conferred by the binding of the KSHV-encoded LANA protein to the viral terminal repeats (TR).

106 the major viral latency transcripts encoding LANA as well as the viral miRNAs and thus has the potent

107 Here, we have examined LANA interactions with host chromatin on a genome-wide s

108 As expected, LANA mutants with alanine or glutamate substitutions in

109 urine gammaherpesvirus 68 chimera expressing LANA, where the virus was highly deficient in establishi

110 oma-associated herpesvirus (KSHV) expressing LANA with a deletion of aa 1100 to 1150 (BAC16Delta1100-

111 hyperplasia and lymphoma in mice expressing LANA.

112 HeLa cell nuclear extracts stably expressing LANA and was verified by coimmunoprecipitation analyses

113 h an interaction with LANA which facilitates LANA sequestration away from KSHV episomes during reacti

114 l screening cascade and identified the first LANA binders from small, structurally diverse compound l

115 in which purified, adenovirus-expressed Flag-LANA protein was incubated with an array displaying 4,19

116 the substitution mutants were deficient for LANA DNA replication and episome maintenance.

117 rf2 association, while Nrf2 is essential for LANA-1 and KAP1 recruitment to the ORF50 promoter and it

118 These studies support a role for LANA in regulating KSHV replication through posttranslat

119 cted B cells with CD4(+)T cells specific for LANA, a protein expressed in all KSHV-infected cells and

120 influenced the expression of the latent gene LANA nor affected KSHV infectivity.

121 substitutions in Kaposi sarcoma herpesvirus LANA and prototype foamy virus chromatin-binding sequenc

122 These host LANA-binding sites are generally found within transcript

123 en extensively studied, the mechanism of how LANA escapes host's immune surveillance is not fully und

124 However, LANA expression in telomerase immortalized endothelial c

125 In a previous study, we have identified LANA-interacting proteins using a protein array screen.

126 f LANA to block viral persistence.IMPORTANCE LANA-mediated latent DNA replication is essential for ef

127 ures to regulate LANA translation.IMPORTANCE LANA, the most abundantly expressed protein during laten

128 A significant decrease in LANA-1 expression, an increase in lytic gene expression,

129 abilizing ligand to define the inhibition in LANA expression and presentation on the cell surface thr

130 the functional role of the positive patch in LANA-mediated episome persistence.

131 ition through formation of G-quadruplexes in LANA mRNA.

132 ddition, we mapped a 50-amino acid region in LANA which was capable of abrogating the association of

133 the electrostatic patch exerts a key role in LANA-mediated DNA replication and episome persistence an

134 nternal LANA regions exert critical roles in LANA-mediated DNA replication, segregation, and episome

135 the formation of these stable structures in LANA mRNA inhibits its translation to control antigen pr

136 esses multiple viral latent genes, including LANA, vFLIP, vCYC, all viral micro RNAs, and kaposin und

137 Tim depletion inhibited LANA-dependent TR DNA replication and caused the loss of

138 methylation of H3K9 significantly inhibited LANA binding to the histone H3 tail.

139 Our research shows that intact LANA traffics to the cytoplasm of cells undergoing permi

140 This is mediated by two interactions: LANA binds to specific sequences (LBS1 and LBS2) on vira

141 Interestingly, LANA enhanced the degradation of some RLIM substrates, s

142 Interestingly, LANA expression ablated RPA1 and RPA2 binding to the cel

143 Interestingly, LANA-1 is crucial for efficient KAP1/Nrf2 association, w

144 Internal LANA sequence upstream of the internal repeat elements c

145 t sufficient, since deletion of all internal LANA sequence renders LANA highly deficient for episome

146 ecently showed that deletion of all internal LANA sequences results in highly deficient episome maint

147 Here we assess independent internal LANA regions for effects on episome persistence.

148 These data suggest that internal LANA regions exert critical roles in LANA-mediated DNA r

149 Here, we investigate LANA sequence upstream of the internal repeat elements t

150 These experiments expand the known LANA-binding proteins to include MHV68 lytic replication

151 ture, we found that apart from the two known LANA binding sites, LBS1 and LBS2, LANA also binds to a

152 KSHV LANA alone can induce the development of B-cell hyperpla

153 EBNA1(ARF) encodes a KSHV LANA-like glutamine- and glutamic acid-rich protein, whe

154 demonstrate the feasibility of using a KSHV LANA-targeted CRISPR-Cas9 and adenoviral delivery system

155 dentifies a novel mechanism utilized by KSHV LANA to deregulate MHC-II gene expression, which is crit

156 e generated an MHV68 virus that encodes KSHV LANA (kLANA) in place of MHV68 LANA (mLANA) and evaluate

157 segregation and persistence.IMPORTANCE KSHV LANA mediates episomal persistence of viral genomes.

158 19 interactions previously reported in KSHV LANA interaction studies.

159 Instead, KSHV LANA recruits the host cell DNA replication machinery to

160 While previous studies of KSHV LANA defined interactions with host cell proteins that i

161 Significantly, KSHV LANA mutants lacking the acidic domain reader sequence a

162 We show that KSHV LANA and MHV-68 LANA proteins bind LBS DNA using strikin

163 we report the crystal structure of the KSHV LANA DNA-binding domain (DBD) in complex with its high-a

164 ecombinant MHV68 virus that encodes the KSHV LANA protein in place of the MHV68 LANA homolog.

165 We determined that the KSHV LANA protein is capable of supporting MHV68 latency in a

166 in sequence, structure, and function to KSHV LANA (kLANA), thereby allowing the study of LANA-mediate

167 posi's sarcoma-associated herpesvirus (KSHV) LANA protein is essential for the replication and mainte

168 Rescue by a larger LANA peptide, LANA(1-32), required second-site mutations

169 During latency, LANA localizes to discrete punctate spots in the nucleus

170 During latency, LANA localizes to the nucleus, where it connects viral a

171 two known LANA binding sites, LBS1 and LBS2, LANA also binds to a novel site, denoted LBS3.

172 ernative mechanism for telomere maintenance, LANA expression had minimal effect on telomere length.

173 of KSHV episomes during mitosis, which makes LANA an ideal target for CRISPR-Cas9 editing.

174 ns (mBFP2-ORF6, mCardinal-ORF52, and mCherry-LANA).

175 We sought to determine if KSHV and MHV68 LANA homologs are functionally interchangeable.

176 encodes KSHV LANA (kLANA) in place of MHV68 LANA (mLANA) and evaluated the virus's capacity to repli

177 We previously demonstrated that MHV68 LANA (mLANA) is required for efficient lytic replication

178 viral proteins that interact with the MHV68 LANA homolog during lytic infection.

179 the KSHV LANA protein in place of the MHV68 LANA homolog.

180 haracteristic subnuclear KSHV microdomains ("LANA speckles"), a hallmark of KSHV latency.

181 ed episome maintenance protein (EMP), namely LANA (KSHV), EBNA1 (EBV), and E2 (HPV).

182 ressed viral proteins found in PELs, namely, LANA and viral IRF3 (vIRF3), albeit at lower levels, wit

183 protein, encoded by the RNF12 gene), a novel LANA-interacting protein identified in that protein scre

184 To identify novel LANA protein-cell protein interactions that could contri

185 , these results suggest that activated Nrf2, LANA-1, and KAP1 assemble on the ORF50 promoter in a tem

186 from that of ET domain recognition of NSD3, LANA of herpesvirus, and integrase of MLV, which involve

187 translocation resulted in decreased nuclear LANA-1 and ANG levels, decreased interactions between AN

188 rylation was not dependent on the ability of LANA to drive KSHV-infected cells into S-phase.

189 l sequence exerted effects on the ability of LANA to retain green fluorescent protein (GFP) expressio

190 ression decreased the promoter activities of LANA-regulated genes.

191 ght confer potential in vivo applications of LANA-specific Cas9 against KSHV infection and KS.IMPORTA

192 r assemblies involve the self-association of LANA into supermolecular spirals.

193 Most surprisingly, the association of LANA to both host and viral DNA is strongly disrupted du

194 s therefore suggests that the association of LANA to chromatin during a productive infection cycle is

195 ur binding assays revealed an association of LANA with NAP1L1 in KSHV-infected cells, which binds thr

196 Thus, H2AX contributes to association of LANA with the TRs, and phosphorylation of H2AX is likely

197 ructure, oligomerization, and DNA binding of LANA have evolved differently to assemble on the TR DNA.

198 n H2AX levels resulted in reduced binding of LANA with KSHV terminal repeats (TRs).

199 enome regulation via a complex consisting of LANA and the H3K9me1/2 histone demethylase JMJD1A/KDM3A.

200 ent sites of the complex, while depletion of LANA expression or overexpression of a KDM3A binding-def

201 ntial for targeting the C-terminal domain of LANA to block viral persistence.IMPORTANCE LANA-mediated

202 the amino- and carboxyl-terminal domains of LANA.

203 Here, we explore the effect of LANA on the stability and activity of RLIM (RING finger

204 Additionally, the expression of LANA in a luciferase promoter reporter assay showed redu

205 Expression of LANA leads to downregulation of RLIM protein levels.

206 We hypothesize that cytoplasmic forms of LANA, whose expression increases during lytic replicatio

207 ytic replication and extends the function of LANA from its role during latency to the lytic replicati

208 onarily conserved and divergent functions of LANA homologs in Rhadinovirus infection and disease.

209 Even though the functions of LANA in aiding pathogenesis of the virus have been exten

210 development of pharmacological inhibitors of LANA E3 ubiquitin ligase activity may allow strategies t

211 Conversely, the interaction of LANA with an acetylation-deficient p53 mutant is enhance

212 ed to the conclusion that the interaction of LANA with RFX proteins interferes with the recruitment o

213 ovel function of the cytoplasmic isoforms of LANA during lytic replication and extends the function o

214 evealed the presence of multiple isoforms of LANA in the cytoplasm of ORF50/RTA-activated Vero cells

215 terminally truncated cytoplasmic isoforms of LANA, resulting from internal translation initiation, ha

216 mmune detection by maintaining the levels of LANA protein below a threshold required for detection by

217 rnal regions did not reduce the half-life of LANA.

218 or regulation of the nuclear localization of LANA will enhance our understanding of the biology of th

219 In this study, we identified a mechanism of LANA expression and restricted immune recognition throug

220 RFX proteins and that the overexpression of LANA disrupts the association of CIITA with the MHC-II p

221 , we investigate this region with a panel of LANA deletion mutants.

222 We generated a panel of LANA mutants that included deletions in the large intern

223 The N-terminal region of LANA binds histones H2A and H2B to attach to mitotic chr

224 Both the N- and C-terminal regions of LANA are essential for episome persistence.

225 We defined the autoregulatory role of LANA and identified a cellular RNA helicase, hnRNP A1, r

226 dy sheds light on the autoregulatory role of LANA to modulate its expression and immune evasion throu

227 Solution structure of LANA complexes revealed that while kLANA tetramer is int

228 LANA (kLANA), thereby allowing the study of LANA-mediated pathogenesis in mice.

229 Notably, the C terminus of LANA contributed to phosphorylation of H2AX.

230 These results suggest that trafficking of LANA to different subcellular locations is a regulated p

231 ase, hnRNP A1, regulating the translation of LANA mRNA.

232 program; however, it had a minimal effect on LANA expression and KSHV infectivity.

233 or the controlled nucleation of higher-order LANA oligomers that might contribute to the characterist

234 Rescue by a larger LANA peptide, LANA(1-32), required second-site mutations that are pred

235 osome maintenance (MCM) complex as potential LANA-interacting proteins.

236 We report that PAN RNA promotes LANA-episome disassociation through an interaction with

237 AP1 and the viral latency-associated protein LANA-1 to mediate global lytic gene repression and thus

238 k represents a report of KSHV latent protein LANA and its interactions with AK-B leading to induction

239 an papillomavirus E6 and HIV-1 TAT proteins, LANA did not reduce TIP60 stability.

240 tion of most of this sequence did not reduce LANA's ability to mediate DNA replication.

241 th unacetylated p53, as evidenced by reduced LANA interaction after overexpression of CBP, which acet

242 hese stable secondary structures to regulate LANA translation.IMPORTANCE LANA, the most abundantly ex

243 letion of all internal LANA sequence renders LANA highly deficient for episome maintenance.

244 ion assays from NAP1L1-depleted cells showed LANA-mediated recruitment of NAP1L1 at the terminal repe

245 Presence of NAP1L1 stimulated LANA-mediated DNA replication and persistence of a TR-co

246 Amino-terminal LANA attaches to chromosomes by binding histones H2A/H2B

247 Although amino- and carboxy-terminal LANA are essential for episome persistence, they are not

248 nding histones H2A/H2B, and carboxy-terminal LANA contributes to mitotic-chromosome binding.

249 These results confirmed that LANA recruitment of NAP1L1 helps in assembling nucleosom

250 Further studies here demonstrate that LANA-1 and ANG colocalize and coimmunoprecipitate in de

251 ammaherpesvirus 68 (MHV68) demonstrated that LANA is important for acute replication, latency establi

252 ide signal amplification, we determined that LANA localizes to the cytoplasm in different cell types

253 Interestingly, we found that LANA enhanced the degradation of some RLIM substrates, s

254 stability of RLIM substrates, we found that LANA modulates transcription by LHX3-LDB1 complex and su

255 lass II-matched CD4(+)T cells and found that LANA-specific T cells restricted to different epitopes r

256 Here we report that LANA promoted the induction of chromosomal instability a

257 Combined, ChIP-seq and RNA-seq reveal that LANA accumulates at active gene promoters that harbor sp

258 Here, we show that LANA blocks MHC-II gene expression to subvert the host i

259 Here we show that LANA contains two tandem, partially overlapping, acidic

260 Here, we show that LANA directly interacted with H2AX through domains at bo

261 Here we show that LANA interacts with Aurora kinase B (AK-B) and induces p

262 Here, we show that LANA is able to form a complex with PCNA, a critical pro

263 Our data show that LANA is capable of binding to all three components of th

264 roughput sequencing (ChIP-seq) and show that LANA predominantly targets human genes near their transc

265 Here, we show that LANA specifically interacts with the components of the M

266 matin immunoprecipitation assays showed that LANA binds to the MHC-II promoter along with RFX protein

267 The studies showed that LANA can also function to regulate viral replication pri

268 Previously, we showed that LANA encoded by KSHV upregulates expression of survivin,

269 Our results showed that LANA interacted physically with the anaphase-promoting c

270 These results suggest that LANA can dysregulate Bub1 activity, which leads to aberr

271 Taken together, our results suggest that LANA may play a role in regulation of epigenetic marks o

272 the latently infected cells, suggesting that LANA possesses a novel role in regulating KSHV replicati

273 o LANA-mediated degradation, suggesting that LANA promotes RLIM autoubiquitination.

274 This suggests that LANA plays important roles in the cytoplasm and nuclear

275 We also report for the first time that LANA's ability to bind host and viral chromatin is highl

276 se chromatin structures were detected at the LANA, RTA and vIL6 promoters.

277 Introduction of a peptide encompassing the LANA aa 1104 to 1123 reduced MCM6 association with LANA

278 ding sites in the KSHV genome, including the LANA promoter region.

279 The structure of the LANA DNA binding domain was recently solved, revealing a

280 Moreover, we show that the LANA DBD can coat DNA of arbitrary sequence by virtue of

281 nsus DNA sequence virtually identical to the LANA-binding site 1 (LBS1) motif in KSHV DNA.

282 dy also identified a novel intron within the LANA 5' untranslated region using a splice acceptor at 1

283 Therefore, LANA's acidic domain reader is critical for viral latenc

284 This LANA-mediated RLIM degradation is blocked in the presenc

285 t of MCMs to the replication origins through LANA was demonstrated through chromatin immunoprecipitat

286 A RING finger mutant RLIM is resistant to LANA-mediated degradation, suggesting that LANA promotes

287 mes in cells containing episomes, similar to LANA.

288 However, the precise mechanism underlying LANA-mediated chromosomal instability remains uncharted.

289 HX3-LDB1 complex and suggest additional ways LANA can modulate cellular gene expression.

290 (LBS), but the molecular mechanism by which LANA assembles on the TR remains elusive.

291 However, the mechanism by which LANA mediates replication is uncertain.

292 we also investigated the mechanism by which LANA promoted Bub1 degradation.

293 sults identifying a novel mechanism by which LANA, a latency-associated antigen encoded by KSHV, can

294 To discover ways in which LANA manipulation of these two kinases might impact PEL

295 This interaction of hnRNP A1 with LANA mRNA could be exploited for controlling KSHV latenc

296 in 1-like protein 1 (NAP1L1) associates with LANA.

297 a 1104 to 1123 reduced MCM6 association with LANA and TR replication.

298 me 50 (ORF50) promoter, its association with LANA-1 and KAP1 abrogates this effect.

299 2AX (gammaH2AX) was shown to colocalize with LANA.

300 monstrated that Bub1 can form a complex with LANA and PCNA in KSHV-positive cells.

301 e disassociation through an interaction with LANA which facilitates LANA sequestration away from KSHV

302 e of abrogating the association of MCM6 with LANA and blocking DNA replication.