ライフサイエンスコーパス: SAMHD1

1 eoxynucleoside triphosphate phosphohydrolase SAMHD1.

2 nd increases the antiviral active isoform of SAMHD1.

3 ours the proteasome-dependent degradation of SAMHD1.

4 TM2 and suppressed expression of RNase L and SAMHD1.

5 x protein of HIV-2 and most SIVs counteracts SAMHD1.

6 HIV-1 infection in macrophages by regulating SAMHD1.

7 plasm, induce the proteasomal degradation of SAMHD1.

8 and N-terminal and SAM domains from mandrill SAMHD1.

9 s, and this effect is lost in the absence of SAMHD1.

10 ely suppressing DC maturation independent of SAMHD1.

11 ecures CRL4 to degrade the antiviral protein SAMHD1.

12 AF1 and the carboxy-terminal region of human SAMHD1.

13 s not counteract restriction factors such as SAMHD1.

14 s the implications of these new functions of SAMHD1.

15 d macrophages despite the restriction factor SAMHD1.

16 roRNAs miR-181a, miR-30a, and miR-155 in the SAMHD1 3'-UTR.

17 de-like 3 (APOBEC3) cytidine deaminases, and SAMHD1 (a cell cycle-regulated dNTP triphosphohydrolase)

18 idine-aspartate domain-containing protein 1 (SAMHD1), a deoxyribonucleoside triphosphate triphosphohy

19 e-aspartic acid domain-containing protein 1 (SAMHD1), a dNTP triphosphohydrolase, regulates the level

20 ated the influence of the restriction factor SAMHD1, a dNTP hydrolase (dNTPase) and RNase, on HBV rep

21 SAMHD1, a dNTP triphosphohydrolase, contributes to inter

22 SAMHD1 ablation increases the antileukemic activity of d

23 The EC50(dNTP) values for SAMHD1 activation by dNTPs are in the 2-20 mum range, an

24 cells restrictive to retroviral replication, SAMHD1 activation is likely to be achieved through a dis

25 on virus replication, manipulating cellular SAMHD1 activity can significantly enhance or decrease th

26 cers, that these mutations negatively affect SAMHD1 activity, and that several SAMHD1 mutations are f

27 Loss of SAMHD1 activity-through genetic depletion, mutational in

28 a residue that is phosphorylated to regulate SAMHD1 activity.

29 ions in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, or MDA5.

30 In humans, loss of function mutations in the SAMHD1 (AGS5) gene cause a severe form of Aicardi-Goutie

31 TREX1 (AGS1), RNase H2 (AGS2, 3 and 4), and SAMHD1 (AGS5).

32 se embryos revealed that inactivation of one SAMHD1 allele is sufficient to elevate dNTP pools.

33 An in vivo model is suggested where SAMHD1 alternates between the mutually exclusive functio

34 M domain and HD domain-containing protein 1 (SAMHD1), an innate immune factor that suppresses HIV rep

35 The phenotypes associated with loss of samhd1 and adar suggest a function of these genes in con

36 We studied if SAMHD1 and dGK interact in the regulation of the dGTP po

37 Therefore, topoisomerase inhibitors regulate SAMHD1 and HIV permissivity at a post-RT step, revealing

38 iviruses encode accessory proteins that bind SAMHD1 and induce its degradation; in turn, positive div

39 tor and substrate of the triphosphohydrolase SAMHD1 and is subject to SAMHD1-mediated inactivation.

40 t remains independent of restriction factors SAMHD1 and myxovirus resistance 2 (MX2).

41 persistent contaminants that co-purify with SAMHD1 and not from the HD active site.

42 ine triphosphate nucleotidohydrolase induced SAMHD1 and proinflammatory cytokines (eg, interleukin 6,

43 biology of the restriction factors APOBEC3, SAMHD1 and tetherin and the viral accessory proteins tha

44 CRL4) by facilitating an interaction between SAMHD1 and the substrate receptor DDB1- and Cullin4-asso

45 Comparison of the wild-type SAMHD1 and the T592D mutant reveals that the phosphomime

46 cyclin A2, CDK2 phosphorylates T592 of human SAMHD1 and thereby regulates its HIV-1 restriction funct

47 ternative interaction interfaces are used by SAMHD1 and Vpx: the SAMHD1 N-terminal tail and the adjac

48 ctor genes, such as APOBEC3F/G, TRIM5-alpha, SAMHD1, and BST-2.

49 ediating degradation of the antiviral factor SAMHD1, and is conserved among diverse HIV-2/SIV Vpx.

50 the 5'- and 3'-untranslated region (UTR) of SAMHD1, and the mechanism responsible for the cell type-

51 y, infection by HIV-2 and SIVsm encoding the SAMHD1 antagonist Vpx was insensitive to ETO treatment.

52 scular dendritic cells, and macrophages, and SAMHD1 antibodies were prevalent in tertiary lymphoid ti

53 Mutations in SAMHD1 are also implicated in the pathogenesis of chroni

54 Moreover, deleterious polymorphisms in human SAMHD1 are associated with autoimmune disease linked to

55 dNTPase activity and nuclear localization of SAMHD1 are required for its suppression of innate immuni

56 spite the presence of the restriction factor SAMHD1, are unknown.

57 These results identify SAMHD1 as a potential biomarker for the stratification o

58 SAMHD1 can be regulated by dGTP, with which SAMHD1 assembles into catalytically active tetramers.

59 x/Vpr recognizes the host restriction factor SAMHD1 at either its N- or C-terminal tail and targets i

60 in half-life, and optimal phosphorylation of SAMHD1 at Thr(592) Furthermore, we observed that SAMHD1

61 CyclinA2-CDK1/2 phosphorylates SAMHD1 at Thr-592, but how this modification controls SA

62 dies suggested that phosphorylation of human SAMHD1 at threonine 592 by CDK1 and cyclin A2 negatively

63 and CDK2, which mediates phosphorylation of SAMHD1 at threonine 592, a post-translational modificati

64 vel recurrent MCL drivers, including CDKN1B, SAMHD1, BCOR, SYNE1, HNRNPH1, SMARCB1, and DAZAP1.

65 CD4(+) myeloid lineage and resting T-cells, SAMHD1 blocks HIV-1 and other viral infections by deplet

66 and macrophages as well as resting T-cells, SAMHD1 blocks HIV-1 infection through this dNTP triphosp

67 udy, we investigate allosteric activation of SAMHD1 by deoxynucleotide-dependent tetramerization and

68 ate details of clade-specific recognition of SAMHD1 by lentiviral Vpx proteins.

69 Down-regulation of SAMHD1 by siRNA expands all four dNTP pools, with dGTP u

70 We demonstrate that induction of SAMHD1 by type I and II interferons depends on 3'-UTR po

71 e bipartite cyclinA2-CDK-binding site in the SAMHD1 C terminus described herein abolished SAMHD1 phos

72 SAMHD1 can also modulate antibody production in adaptive

73 The dNTPase activity of SAMHD1 can be regulated by dGTP, with which SAMHD1 assem

74 hese processes, the fundamental mechanism of SAMHD1-catalysed dNTP hydrolysis remained unknown.

75 This precise molecular mechanism for SAMHD1 catalysis, reveals how SAMHD1 down-regulates cell

76 Here, we present the crystal structures of SAMHD1 catalytic core (residues 113-626) tetramers, comp

77 ing humans, where the corresponding homolog (SAMHD1) cleaves dNTPs.

78 e infection of T(SCM) cells, indicating that SAMHD1 contributes to abortive infection in these cells.

79 We conclude that the activity of SAMHD1 contributes to the pathological phenotype of dGK

80 MHD1 dNTPase in S phase, thereby fine-tuning SAMHD1 control of dNTP levels during DNA replication.

81 emonstrate that the interaction of CD81 with SAMHD1 controls the metabolic rate of HIV-1 replication

82 ects sooty mangabeys (SIVsmm) complexed with SAMHD1-DCAF1 identifies molecular determinants directing

83 reak-point junctions is a notable feature in SAMHD1 deficiency during activation-induced cytidine dea

84 Moreover, Vpx enhanced HIV-1 infection of SAMHD1-deficient resting CD4 T cells of a patient with A

85 diamine (TPEN) potently blocked Vpx-mediated SAMHD1 degradation and inhibited wild-type SIVmac (simia

86 viral replication, Vpx has evolved to induce SAMHD1 degradation and Vpr to mediate HLTF degradation.

87 dent on the presence of DCAF1 and results in SAMHD1 degradation in a proteasome- and DCAF1-dependent

88 , and, unexpectedly, acted in the absence of SAMHD1 degradation, dNTP pool elevation, or changes in S

89 the CRL4 (DCAF1) E3 complex and Vpx-induced SAMHD1 degradation.

90 d in the virion and is dedicated to inducing SAMHD1 degradation.

91 Single amino acid changes in the SAMHD1-degrading Vpx mac239 allowed it to enhance early

92 V-1 replication in vivo Finally, we reveal a SAMHD1-dependent antiretroviral activity of histone deac

93 SAMHD1-dependent dNTP depletion is thought to impair ret

94 f p53, p21, decrease in CDK1 expression, and SAMHD1 dephosphorylation.

95 Notably, higher infection observed with SAMHD1 depletion correlated with a stronger suppression

96 , double-stranded DNA breaks was impaired by SAMHD1 depletion, which was accompanied by enhanced nucl

97 ous disparate findings regarding the site of SAMHD1 depletion.

98 ore, our finding that intracellular CUL4 and SAMHD1 distributions can vary with cell type provides th

99 -592 phosphorylation state to the control of SAMHD1 dNTPase activity.

100 CDK down-modulates, but does not inactivate, SAMHD1 dNTPase in S phase, thereby fine-tuning SAMHD1 co

101 revented SAMHD1 phosphorylation and promoted SAMHD1 dNTPase-independent antiviral activity.

102 Thus, SAMHD1 does not appear to play a key role in the inducti

103 ed Langerhans cells (LC), but degradation of SAMHD1 does not rescue HIV-1 or vesicular stomatitis vir

104 mechanism for SAMHD1 catalysis, reveals how SAMHD1 down-regulates cellular dNTP and modulates the ef

105 es revealed that the host restriction factor SAMHD1 exists in a hyperphosphorylated, less active stat

106 uggest the contribution of cyclin binding to SAMHD1 expression and stability in dividing cells.

107 from AML patients at diagnosis revealed that SAMHD1 expression in leukemic cells inversely correlates

108 SAMHD1 expression is differentially regulated by interfe

109 aining therapy was inversely correlated with SAMHD1 expression.

110 y testing whether evolutionary signatures in SAMHD1 extend to other mammalian groups and exploring th

111 via the accessory protein Vpx, which targets SAMHD1 for degradation through interactions with the hos

112 ich normally does not target wild type human SAMHD1 for degradation.

113 /HIV-2) lineage packaged into virions target SAMHD1 for proteasomal degradation, increase intracellul

114 the host cullin-4 ubiquitin ligase to target SAMHD1 for proteasomal degradation.

115 iral protein r (Vpr) that target and recruit SAMHD1 for proteasomal degradation.

116 sociated factor 1 (DCAF1), thereby targeting SAMHD1 for proteasome-dependent down-regulation.

117 Cyclin L2 and SAMHD1 form a molecular complex that is partially depend

118 SAMHD1 forms tetramers that possess deoxyribonucleotide

119 The deoxyguanosine released by SAMHD1 from dGTP can be phosphorylated inside mitochondr

120 presented here advance our understanding of SAMHD1 function during cellular homeostasis.

121 SAMHD1 functions as an important retroviral restriction

122 Thr-592, but how this modification controls SAMHD1 functions in proliferating cells is not known.

123 volutionary pressures affect these different SAMHD1 functions.

124 expresses a green fluorescent protein (GFP)-SAMHD1 fusion protein, we showed that the Vpx-dependent

125 The host protein SAMHD1 has been identified as the first mammalian deoxyn

126 SAMHD1 has been reported to be able to degrade dNTPs and

127 lentiviral proteins, suggesting that primate SAMHD1 has coevolved to evade these countermeasures.

128 M domain and HD domain-containing protein 1 (SAMHD1) has been identified as a restriction factor, low

129 To overcome SAMHD1, HIV-2 and some SIVs encode either of two lineage

130 of the sterile alpha motif and HD domain 1 (SAMHD1) host restriction factor by the HIV-2 Vpx gene pr

131 Mechanistically, dGTP-activated SAMHD1 hydrolyzes Ara-CTP, which results in a drastic re

132 Sequence analysis of SAMHD1 identifies a putative cyclin-binding motif found

133 Depletion of SAMHD1 impaired not only CSR but also IgH/c-Myc transloc

134 HIV-1 and HIV-2 with DNA repair enzymes and SAMHD1 imply that these viruses use different strategies

135 WT SAMHD1 in differentiated U937 cells significantly inhibi

136 We demonstrated that silencing of SAMHD1 in hepatic cells increased HBV replication, while

137 Depletion of SAMHD1 in macrophages decouples the association between

138 block was completely rescued by depletion of SAMHD1 in MDM Concordantly, infection by HIV-2 and SIVsm

139 HIV-1 replication, the antiviral activity of SAMHD1 in our primary cell model appears to be, at least

140 y further defines the role and mechanisms of SAMHD1 in suppressing innate immunity.

141 ine derived from endogenous dGTP degraded by SAMHD1 in the nucleus.

142 Our results prove the importance of SAMHD1 in the regulation of all dNTP pools and suggest t

143 understanding of the important functions of SAMHD1 in the regulation of cellular dNTP levels, as wel

144 Consequently, CD81 depletion results in SAMHD1 increased expression, decreasing the availability

145 siRNA silencing of SAMHD1 increases dNTP pools, stops cycling human cells i

146 In conclusion, we report a SAMHD1-independent post-entry restriction in MDLC and LC

147 ibited Vpx and DCAF1 binding but not the Vpx-SAMHD1 interaction or Vpx virion packaging.

148 We and others have reported that human SAMHD1 interacts with the cell cycle regulatory proteins

149 Together, our data suggest that SAMHD1 is a biomarker for the stratified use of hypometh

150 SAMHD1 is a cellular protein that plays key roles in HIV

151 SAMHD1 is a deoxynucleoside triphosphate (dNTP) triphosp

152 SAMHD1 is a dNTP hydrolase, whose activity is required f

153 SAMHD1 is a host triphosphohydrolase that degrades intra

154 ynucleoside triphosphate triphosphohydrolase SAMHD1 is a myeloid cell-specific retroviral restriction

155 These results suggest that SAMHD1 is a non-classical interferon-stimulated gene reg

156 The dNTP triphosphohydrolase SAMHD1 is a nuclear antiviral host restriction factor li

157 SAMHD1 is a nuclear deoxyribonucleoside triphosphate tri

158 SAMHD1 is a phosphohydrolase maintaining cellular dNTP h

159 These results suggest that SAMHD1 is a relevant restriction factor for HBV and rest

160 The HIV-1 restriction factor SAMHD1 is a tetrameric enzyme activated by guanine nucle

161 lization approaches, we show that endogenous SAMHD1 is able to interact with the cyclin A-CDK1-CDK2 c

162 Tetrameric SAMHD1 is activated for the hydrolysis of any dNTP only

163 Here we show that SAMHD1 is also expressed in epidermis-isolated Langerhan

164 f this CD4(+) T cell subset, indicating that SAMHD1 is an active restriction factor in T(SCM) cells.

165 We conclude that SAMHD1 is an essential modulator of infectivity in a sex

166 SAMHD1 is an intracellular enzyme that specifically degr

167 FP.SAM595 in which the Vpx binding domain of SAMHD1 is fused to the carboxy terminus of green fluores

168 The vertebrate protein SAMHD1 is highly unusual in having roles in cellular met

169 lls, indicating that the dNTPase activity of SAMHD1 is important for suppressing NF-kappaB activation

170 Although the physiological function of SAMHD1 is largely unknown, this review provides perspect

171 The anti-HIV-1 activity of SAMHD1 is negatively modulated by phosphorylation at res

172 Thus, cellular regulation of active SAMHD1 is not determined by GTP alone but instead, the l

173 findings help define the mechanisms by which SAMHD1 is phosphorylated and suggest the contribution of

174 The restriction ability of SAMHD1 is regulated in cells by phosphorylation on T592.

175 nd we hypothesize that enzymatic activity of SAMHD1 is subject to additional cellular regulatory mech

176 ontroversial whether the dNTPase activity of SAMHD1 is sufficient for restriction.

177 as localized to the nucleus, confirming that SAMHD1 is targeted in the nucleus and thus explaining wh

178 to Vpx-mediated degradation, confirming that SAMHD1 is targeted in the nucleus.

179 ha motif and HD domain-containing protein 1 (SAMHD1) is a deoxynucleoside triphosphohydrolase (dNTPas

180 domain- and HD domain-containing protein 1 (SAMHD1) is proposed to inhibit HIV-1 replication by depl

181 se activity, but not nuclear localization of SAMHD1, is important for its suppression of innate immun

182 ool of dNTPs, implying that VEN4, like human SAMHD1, is involved in dNTP catabolism.

183 Therefore, cyclin L2-mediated control of SAMHD1 levels in macrophages supports HIV-1 replication.

184 Here, we show that SAMHD1 levels remain relatively unchanged during the cel

185 The restriction factor SAMHD1 limits HIV-1 replication in noncycling cells.

186 We discovered that SAMHD1 localizes at the immunoglobulin (Ig) switch regio

187 ncing of the TP53, SF3B1, ATM, NOTCH1, XPO1, SAMHD1, MED12, BIRC3, and MYD88 genes.

188 We propose that SAMHD1-mediated dNTP balance regulates dNTP-sensitive DN

189 dvance functional and mechanistic studies of SAMHD1-mediated immune regulation during viral infection

190 triphosphohydrolase SAMHD1 and is subject to SAMHD1-mediated inactivation.

191 lar extent as did WT SAMHD1, suggesting that SAMHD1-mediated inhibition of innate immune responses is

192 SAMHD1-mediated retroviral restriction is thought to res

193 cordingly, mtDNA rNMPs were nearly absent in SAMHD1 (-/-) mice that have increased dNTP pools.

194 D1 at Thr(592) Furthermore, we observed that SAMHD1 mutants of the cyclin-binding motif mislocalized

195 exerted by Thr-592 phosphorylation-defective SAMHD1 mutants were associated with activation of DNA da

196 SAMHD1 mutations are associated with the autoimmune dise

197 ely affect SAMHD1 activity, and that several SAMHD1 mutations are found in tumors with defective mism

198 suggest that heterozygous cancer-associated SAMHD1 mutations increase mutation rates in cancer cells

199 SAMHD1 mutations that interfere with the dNTPase activit

200 s of the accessory protein Vpx that bind the SAMHD1 N or C terminus and redirect the host cullin-4 ub

201 details of Vpx lineage-specific targeting of SAMHD1 N-terminal "degron" sequences.

202 n interfaces are used by SAMHD1 and Vpx: the SAMHD1 N-terminal tail and the adjacent SAM domain or th

203 et al. (2015) report the structural basis of SAMHD1 N-terminal targeting by Vpx.

204 Recent progress indicates that SAMHD1 negatively regulates antiviral innate immune resp

205 s are observed in immune cells cultured from Samhd1 null mouse models, these mice are physically heal

206 in human SAMHD1 to Phe, the residue found in SAMHD1 of Red-capped monkey and Mandrill, allows it to b

207 e degradation of the host restriction factor SAMHD1 or host helicase transcription factor (HLTF), res

208 nocytic U937 cell lines stably expressing WT SAMHD1 or mutated variants defective in dNTPase activity

209 Furthermore, loss of samhd1 or of another AGS-associated gene, adar, leads to

210 in a virion also needs to clear the cell of SAMHD1 over a prolonged period of time.

211 se results indicate that Vpx, in addition to SAMHD1, overcomes a previously unappreciated restriction

212 er mutation of the catalytic residues of the SAMHD1 phosphohydrolase domain or by a Thr-592 phosphomi

213 ells and its impact on T cell activation and SAMHD1 phosphorylation (Thr592).

214 In parallel, p21 prevented SAMHD1 phosphorylation and promoted SAMHD1 dNTPase-indep

215 s provide a mechanistic understanding of how SAMHD1 phosphorylation at residue Thr-592 may modulate i

216 SAMHD1 C terminus described herein abolished SAMHD1 phosphorylation on Thr-592 during S and G2 phases

217 n addition, the major kinase responsible for SAMHD1 phosphorylation, CDK1, exhibited lower levels of

218 radation, dNTP pool elevation, or changes in SAMHD1 phosphorylation.

219 idine-aspartate domain-containing protein 1 (SAMHD1) plays a critical role in inhibiting HIV infectio

220 SAMHD1 potently blocks HIV-1 replication in DCs, althoug

221 the trace exonuclease activities detected in SAMHD1 preparations arise from persistent contaminants t

222 SAMHD1 protects cells from invading viruses that depend

223 for the cell type-dependent up-regulation of SAMHD1 protein by interferon.

224 es perspectives about the role of endogenous SAMHD1 protein in maintaining normal cellular function,

225 and miR-30a levels inversely correlates with SAMHD1 protein up-regulation upon type I and II interfer

226 than those seen upon expression of wild type SAMHD1 protein.

227 Human and mouse SAMHD1 proteins block HIV-1 infection in noncycling cell

228 In the presence of SAMHD1 quiescent mutant fibroblasts manifested mt dNTP p

229 letion of competing dNTPs, we show here that SAMHD1 reduces Ara-C cytotoxicity in AML cells.

230 In this review, we summarize how SAMHD1 regulates antiviral immune responses through dist

231 SAMHD1 regulates cellular 2'-deoxynucleoside-5'-triphosp

232 Here, we report that SAMHD1 regulation of the dNTP concentrations influences

233 election may have involved the adaptation of SAMHD1 regulation to balance antiviral, metabolic, and i

234 In particular, SAMHD1-related AGS is associated with a distinctive cere

235 or generating a clinically relevant model of SAMHD1-related AGS.

236 ic cells, and consequently protein levels of SAMHD1 remain unchanged.

237 ificity, while a 7- angstrom cleft separates SAMHD1 residues from dNTP bases, abolishing nucleotide-t

238 Vpx degrades the SAMHD1 restriction factor, potentially reducing abortive

239 ation that has been implicated in abrogating SAMHD1 restriction function and ability to form stable t

240 Interfering with SAMHD1 restriction further increased infection of DCs, b

241 ated simian immunodeficiency viruses (SIVs), SAMHD1 restriction is overcome by the action of viral ac

242 SAMHD1 restricts lentiviral replication in myeloid cells

243 f domain and HD domain-containing protein 1 (SAMHD1) restricts human immunodeficiency virus type 1 (H

244 stidine/aspartate (HD)-containing protein 1 (SAMHD1) restricts human/simian immunodeficiency virus in

245 The depletion of the restriction factor SAMHD1 resulted in a markedly increased number of EdU pu

246 domain- and HD domain-containing protein 1 (SAMHD1) returns to levels below those observed in uninfe

247 we report that AGS gene silencing of TREX1, SAMHD1, RNASEH2A, and ADAR1 by short hairpin RNAs in hum

248 of innate immune responses is independent of SAMHD1's nuclear localization.

249 Furthermore, SAMHD1 sensitises cancer cells to nucleoside-analogue an

250 Although it has been postulated that SAMHD1 sensitizes cancer cells to nucleoside-analog deri

251 s directing Vpx lineages to N- or C-terminal SAMHD1 sequences.

252 despite no sequence homology, Ec-dGTPase and SAMHD1 share similar active-site and HD motif architectu

253 Third, differentiated SAMHD1 shRNA THP-1 cells have a 2-fold increase in HIV-1

254 SAMHD1 significantly affected the levels of extracellula

255 by HIV, and we demonstrate that knockdown of SAMHD1 significantly increases the frequency of infectio

256 Moreover, WT and mutant SAMHD1 similarly interacted with key proteins in NF-kapp

257 SAMHD1 (sterile alpha motif and HD domain-containing pro

258 SAMHD1 (sterile alpha motif and histidine (H) aspartate

259 RNA expression to a similar extent as did WT SAMHD1, suggesting that SAMHD1-mediated inhibition of in

260 SAMHD1 suppresses innate immune responses to viral infec

261 SAMHD1 suppresses viral reverse transcription (RT) throu

262 ting in upregulation of CDK1 with subsequent SAMHD1 T592 phosphorylation and deactivation of its anti

263 mutation T592E reduces the stability of the SAMHD1 tetramer and the dNTPase activity of the enzyme.

264 ults reveal an ordered model for assembly of SAMHD1 tetramer from its inactive monomer and dimer form

265 te the impact of phosphomimetic mutations on SAMHD1 tetramerization and dNTPase activity in vitro.

266 t that the effect of T592 phosphorylation on SAMHD1 tetramerization is not likely to explain the retr

267 ificant decrease in the population of active SAMHD1 tetramers, and hence the dNTPase activity is subs

268 toward canonical dNTPs, such as the dNTPase SAMHD1 that blocks reverse transcription of retroviruses

269 macrophages express a phosphorylated form of SAMHD1 that corresponds with susceptibility to infection

270 rolase-independent, moonlighting function of SAMHD1 that facilitates homologous recombination of DNA

271 y affect protein level or phosphorylation of SAMHD1, the virus upregulated intracellular dATPs.

272 screen using metagenomic sequencing related SAMHD1 to increased expression of human endogenous retro

273 how that changing the single Ser-52 in human SAMHD1 to Phe, the residue found in SAMHD1 of Red-capped

274 We cannot rule out a contribution of SAMHD1 to retroviral restriction in relatively non-permi

275 The contributions of SAMHD1 to retroviral restriction in the central nervous

276 Current evidence indicates that Vpx recruits SAMHD1 to the Cullin4-Ring Finger E3 ubiquitin ligase (C

277 Accordingly, we investigated SAMHD1 transcript abundance and association with the Typ

278 SAMHD1 transcript levels were IFN responsive, increasing

279 In vitro, SAMHD1 transcript was abundant in macaque astrocytes and

280 espite HIV-2 Vpx-mediated degradation of the SAMHD1 transcription factor.

281 Both Type I and II interferons may stimulate SAMHD1 transcription.

282 The SAMHD1 triphosphohydrolase inhibits HIV-1 infection of m

283 s acquire resistance to decitabine partly by SAMHD1 up-regulation.

284 Knockdown of the HIV restriction factor SAMHD1 using Vpx-containing simian immunodeficiency viru

285 ructural and enzymological data showing that SAMHD1 utilises an active site, bi-metallic iron-magnesi

286 sms, we determined the crystal structures of SAMHD1 variants T592E and T592V.

287 We report that SAMHD1 was activated by dephosphorylation following ETO

288 Interestingly, SAMHD1 was dephosphorylated, thus in a potentially antiv

289 Monomeric SAMHD1 was found to bind preferentially to single-strand

290 Elevated SAMHD1 was localized to endothelial cells, perivascular

291 SAMHD1 was purified using three chromatography steps, ov

292 Moreover, HBV restriction by SAMHD1 was rescued by addition of deoxynucleosides.

293 When SAMHD1 was silenced by siRNA transfection the compositio

294 Furthermore, SAMHD1 was upregulated by type I and II interferons in h

295 d histidine-aspartic (HD) domains protein 1 (SAMHD1) was previously identified as a critical post-ent

296 Using temporal gene knockdown of zebrafish samhd1, we observe hindbrain ventricular swelling and br

297 differences in viral restriction imposed by SAMHD1 were abrogated upon its depletion.

298 SAM-domain and HD-domain containing protein (SAMHD1), which depletes free nucleotides, blocking rever

299 tic and nucleotide activator site mutants of SAMHD1 with no dNTPase activity retained the exonuclease

300 lihood models, we find positive selection in SAMHD1 within each mammal lineage for which sequence dat

301 We hypothesized that SAMHD1 would respond to interferon in the SIV-infected C