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1 CypA (Cyclophilin A) is a peptidyl-prolyl isomerase prev
2 CypA antagonists, such as cyclosporines, are potent inhi
3 CypA binds to HCV's nonstructural protein (NS)5A to prom
4 CypA can either promote or inhibit viral infection, depe
5 CypA inhibitors prevented replication of residual HCV in
6 CypA interacts with its substrate via conformational sel
7 CypA modulates HIV-1 virion core detection by this class
8 CypA recognizes specific geometries of the curved lattic
9 CypA was previously reported to be required for the bioc
11 yclophilin A (CypA) chimera resulting from a CypA retrotransposition between exons 7 and 8 of the TRI
13 nemestrina and M. fascicularis identifies a CypA retrotransposition in the 3' untranslated region of
16 of developing AADs, whereas treatment with a CypA inhibitor attenuates aortic dilation by 56% (P = 0.
17 el protein systems, including cyclophilin A (CypA) and the minor allele variant of human alanine:glyo
19 The peptidyl-prolyl isomerase cyclophilin A (CypA) binds a proline-rich loop on the surface of HIV-1
21 ably, in Owl monkeys (omk), a cyclophilin A (CypA) cDNA has been transposed into the TRIM5 locus, res
22 mediated by TRIMCyp, a TRIM5-cyclophilin A (CypA) chimera resulting from a CypA retrotransposition b
23 ve site of the dynamic enzyme cyclophilin A (CypA) has been previously linked to its catalytic functi
25 ex in which HCV NS5A and host cyclophilin A (CypA) have been shown to be present together with the vi
26 f the CA-binding host protein cyclophilin A (CypA) inhibited HIV-1 uncoating and reduced the stimulat
29 d in cell lines indicate that cyclophilin A (CypA) is a component of HIV type 1 (HIV-1) virions, and
33 cis-trans isomerase (PPIase) cyclophilin A (CypA) is hijacked by Listeria at membrane protrusions us
36 Recent studies showed that cyclophilin A (CypA) promotes NF-kappaB/p65 nuclear translocation, resu
38 yl prolyl cis/trans isomerase cyclophilin A (CypA) serves as a cellular receptor for the important im
39 Herein, we identify a novel Cyclophilin A (CypA) small molecule inhibitor (HL001) that induces non-
44 eractions with both CPSF6 and cyclophilin A (CypA) were essential for the unique dose-response curve.
45 Also, virion incorporation of cyclophilin A (CypA), a cellular peptidyl-prolyl isomerase that binds s
49 20-kDa protein, identified as cyclophilin A (CypA), and CypA was present on the surface of Hc yeasts.
50 al inhibition or silencing of cyclophilin A (CypA), as well as CA mutant viruses, we implicated CypA
51 d with host cell factors like cyclophilin A (CypA), can influence the efficiency of reverse transcrip
52 viral lifecycle by utilising cyclophilin A (CypA), cleavage and polyadenylation specificity factor-6
53 essential cellular co-factor cyclophilin A (CypA), HCV RNA replication is markedly diminished, provi
54 ablation and/or inhibition of cyclophilin A (CypA), here we show that expression of APOE4 and lack of
55 cs simulations to study human cyclophilin A (CypA), in order to understand the role of enzyme motions
56 ificity factor 6 (CPSF6), and cyclophilin A (CypA), indicating that the observed loss of sensitivity
57 ects of the host cell protein cyclophilin A (CypA), which binds to HIV-1 CA, on HIV-1 infection of no
58 ptidyl-prolyl isomerase (PPI) cyclophilin A (CypA), which is implicated in the regulation of protein
59 9), I(223), and M(228) in the cyclophilin A (CypA)-binding loop in B57(+) individuals with progressiv
60 tor 6 (CPSF6), as well as the cyclophilin A (CypA)-binding loop mutation P90A, all increase sensitivi
76 Because core-binding factor subunit beta and CypA are both highly conserved among mammals, the requir
78 he known binding interaction between CsA and CypA was detected using both the MALDI- and LC-MS-based
80 ample containing NS5B(Delta21), NS5A-D2, and CypA specifically inhibits the interaction between CypA
85 bunit 6 (CPSF6) and cyclophilins (Nup358 and CypA), respectively, cannot replicate in primary human m
89 ization of the surrounding prolines that are CypA substrates and by substitutions conferring resistan
90 pecifically inhibits the interaction between CypA and NS5A-D2 without altering the one between NS5A-D
91 ermolecular hydrophobic interactions between CypA and the substrate, an intricate enzyme-substrate in
94 This activity required capsid binding by CypA and correlated with CypA linkage to the TRIM5a caps
102 vity was not altered by disruption of the CA-CypA interaction or by elimination of CypA protein.
103 ls, we demonstrate that disruption of the CA-CypA interaction renders HIV-1 susceptible to potent res
104 wer drug concentrations upon blocking the CA-CypA interaction suggests a protective role for CypA aga
106 depending on the capsid and the target cell, CypA-CA binding either stabilized or destabilized the ca
110 g ability of a retrotransposed CyclophilinA (CypA), resulting in novel antiviral specificity against
115 tidyl-prolyl isomerase A (PPIA) that encodes CypA on HCV infection and replication of human hepatocyt
118 VSMC-derived intracellular and extracellular CypA are required for ROS generation and matrix metallop
119 ne motif in the helix 4-5 loop important for CypA binding; instead, the helix 4-5 loop in these SIVs
120 Antagonism of the extracellular receptor for CypA (CD147) also reduced acetaminophen-induced liver in
123 ata define a previously undescribed role for CypA in AAA formation and suggest CypA as a new target f
124 le in HIV-1 CA assemblies in the escape from CypA dependence, by magic-angle spinning (MAS) NMR and m
128 d the dynamics profiles of the A92E and G94D CypA escape mutants closely resemble that of wild-type C
129 R spectra of wild-type and the A92E and G94D CypA escape mutants, we demonstrate that assembled CA is
132 ) has been known for nearly two decades, how CypA interacts with the viral capsid and modulates HIV-1
133 These results provide new insights into how CypA stabilizes the HIV-1 capsid and is recruited to fac
134 orescence polarization-based assay for human CypA that can be adapted to high-throughput screening fo
136 el vif-sensitive antiviral activity of human CypA that may limit zoonotic transmission of SIV and the
137 eled cyclosporin A analog and purified human CypA to quantitatively measure the binding capacity of u
139 of the SP1 tail, the functionally important CypA loop, and the loop preceding helix 8 are modulated
140 show that many alternative conformations in CypA are populated only at 240 K and above, yet others r
142 pecific PCR revealed DNA hypermethylation in CypA-KD P19 cells, as the normally unmethylated paternal
143 x9 and Runx2 were all significantly lower in CypA knockdown chondrogenic cells than in wild-type cell
145 ication flow through the distinct regions in CypA and, therefore, as targets for future mutational st
147 es than in other cell types, we investigated CypA and CsA activities in HIV-1-infected primary human
149 ion of phenotype in cyclophilin A knockdown (CypA-KD) P19 cells, we observed a silent paternally expr
150 Our data demonstrated that mice lacking CypA (Ppia(-/-)) were resistant to acetaminophen toxicit
152 is required during uncoating for maintaining CypA-CA interaction, which promotes optimal stability of
153 support HCV replication, finding that murine CypA only partially rescued viral replication in Huh7.5-
156 icted phenotype also restored the ability of CypA-restricted HIV-1 mutants to infect growth-arrested
157 s observed between the levels or activity of CypA and the extent of PRL-induced signaling and gene ex
158 r the isomerase or the chaperone activity of CypA to replicate in hepatocytes and that CypA is the pr
160 ransformed cells and show that the amount of CypA incorporated into virions is variable and that CsA
161 In contrast, reduction of the binding of CypA to HIV-1 capsids in Jurkat T lymphocytes resulted i
163 es as a ligand for DC VLA-5, that binding of CypA to VLA-5 is at a site different from FN, and that t
166 nally important alternative conformations of CypA, confirming earlier synchrotron-based results.
167 e evidence for the important contribution of CypA as a pertinent component acting through NF-kappaB-S
168 ission of SIV and the first demonstration of CypA encapsidation into a virus other than human immunod
170 Cores isolated from WT virus depleted of CypA had an unstable-core phenotype, confirming a role o
171 their proper formation, as cells depleted of CypA have extended actin-rich structures that are missha
179 es of SIVagm Vif to inhibit encapsidation of CypA and to increase viral infectivity were shared by rh
180 e we compare the conformational ensembles of CypA by multitemperature synchrotron crystallography and
182 demonstration of the epigenetic function of CypA in protecting the paternal allele of Peg3 from DNA
185 tion network, connectivity, and influence of CypA residues upon substrate binding, mutation, and duri
186 emonstrates that pharmacologic inhibition of CypA offers a potential therapeutic strategy via specifi
194 ues that reside in the hydrophobic pocket of CypA where proline-containing peptide substrates and cyc
198 n of the speedup in rates in the presence of CypA, which is in notable agreement with experimental es
200 lve the long-standing mystery of the role of CypA in HIV-1 replication by demonstrating that this ubi
203 e cells) and aortas had greater secretion of CypA both at baseline and in response to Ang II stimulat
211 duced dependence of the compensated virus on CypA that is normally essential for optimal infectivity.
218 BB breakdown by activating a proinflammatory CypA-nuclear factor-kappaB-matrix-metalloproteinase-9 pa
220 titis C virus (HCV) co-opts the host protein CypA to aid evasion of antiviral responses dependent on
226 e CypA-binding pattern is achieved by single-CypA molecules simultaneously interacting with two CA su
227 d role for CypA in AAA formation and suggest CypA as a new target for treating cardiovascular disease
231 -sensitive host cell cyclophilins other than CypA contribute to the activity of IFN-alpha-induced blo
233 of CypA to replicate in hepatocytes and that CypA is the principal mediator of the Cyp inhibitor anti
241 lls than in wild-type cells, indicating that CypA plays a functional role in chondrogenic differentia
242 observations argue against the proposal that CypA binding is coupled with beta-hairpin formation and
243 Additional in vitro studies revealed that CypA, Roc1, and Roc2 cyclophilins bound to the viral rep
248 Genetic and biochemical data suggest that CypA protects HIV-1 from a CA-specific restriction facto
249 th previous reports, these data suggest that CypA protects HIV-1 from an unknown antiviral activity i
253 The variants appeared to destabilize the CypA protein; the single amino acid changes led to rapid
255 that is partially overcome by changes in the CypA-binding loop and identify a mechanism for an HIV-1
256 ntified two mutations, A92E and G94D, in the CypA-binding loop of CA that confer the ability of HIV-1
259 pharmacological or genetic disruption of the CypA-CA interaction or by RNA interference-mediated depl
262 The 1.38 angstrom crystal structure of the CypA/PreNAC complex displays a contact between alanine 5
264 ts indicate that CA determinants outside the CypA-binding loop can modulate the dependence of HIV-1 i
266 ecreted APOE3, but not APOE4, suppressed the CypA-nuclear factor-kappaB-matrix-metalloproteinase-9 pa
267 and solid-state NMR further reveal that the CypA-binding pattern is achieved by single-CypA molecule
269 nstructs, we illustrate the ability of these CypA loop changes to partially restore replication of th
272 reduced binding of CD147-derived peptides to CypA and also diminished transport of CD147 to the plasm
274 ive at inhibiting leukocyte migration toward CypA in vitro as well as in the recruitment of leukocyte
276 teasome inhibition prevented owl monkey TRIM-CypA restriction of HIV-1 reverse transcription, even th
278 losporine (CsA) washout assay, in which TRIM-CypA-mediated restriction of viral replication is used t
283 nimals coexpressing the TRIM5(TFP) and TRIM5(CypA) alleles took significantly longer to become infect
284 ocus, resulting in the expression of a TRIM5-CypA fusion protein (TRIMCyp) that restricts retroviral
285 ) and multiple, independently derived, TRIM5-CypA fusion genes(4,5,15,22-26) pointed to human TRIM5al
287 B2 assembly is significantly attenuated upon CypA binding, and the dynamics profiles of the A92E and
291 of HIV type 1 (HIV-1) virions, and that when CypA incorporation into virions is inhibited by treatmen
292 its a distinct CypA-binding pattern in which CypA selectively bridges the two CA hexamers along the d
294 We find that Vpr coimmunoprecipitates with CypA and that this interaction is disrupted by substitut
295 luorescence polarization in combination with CypA is highly advantageous for the accurate assessment
297 d capsid binding by CypA and correlated with CypA linkage to the TRIM5a capsid-specificity determinan
298 esults, we propose that the interaction with CypA is independent of the ability of Vpr to induce cell
299 EC conditioned media, and preincubation with CypA augmented Ang II-induced vascular smooth muscle cel