ライフサイエンスコーパス: SIRT2

1 th Golgi matrix proteins and is regulated by SIRT2.

2 H]AziPm photolabeling of this site in myelin SIRT2.

3 trol of the sirtuin family members SIRT1 and SIRT2.

4 he class III histone deacetylases, SIRT1 and SIRT2.

5 ta was proposed based on a homology model of SIRT2.

6 mechanism mediated redundantly by Sirt1 and Sirt2.

7 on from Sirt1 and increased association with Sirt2.

8 es act as potent and selective inhibitors of SIRT2.

9 ted upon hyperglycemia and down-regulated by SIRT2.

10 ified to develop low nanomolar inhibitors of SIRT2.

11 uctures of compound complexes with Sirt6 and Sirt2.

12 h good potency and excellent selectivity for SIRT2.

13 quently used to select for ligands that bind SIRT2.

14 cture of one of our compounds (29c) bound to SIRT2.

15 ream kinase of AMPK, as the direct target of SIRT2.

16 N-terminus, whereas drug-like activators for Sirt2-7 are lacking.

17 g and kinase assays, we show that sirtuin 2 (SIRT2), a member of the NAD-dependent protein deacetylas

18 Sirtuin 2 (SIRT2), a NAD(+)-dependent deacetylase, bound TUG and de

19 Previous studies have found that SIRT2, a deacetylase, plays an important role in deacety

20 In PAL experiments with SIRT2, a tryptic peptide originating from the covalent a

21 SIRT2, a tumor suppressor gene, contributes to the contr

22 SIRT2 accumulated in the nuclei of dorsal root ganglion

23 eature of mammalian sirtuins, that SIRT1 and SIRT2 act as efficient decrotonylases, and that SIRT1, S

24 However, the mechanism underlying both SIRT2 activation and regulation of the G2-to-M transitio

25 ing CIPN, warranting future investigation of SIRT2 activation-mediated neuroprotection during platinu

26 cells with up-regulated PI3K activity and of Sirt2 activators in the treatment of insulin-resistant m

27 inhibitors, one compound exhibited high anti-SIRT2 activity (48 nM) and excellent selectivity for SIR

28 odegeneration, which makes the modulation of Sirt2 activity a promising strategy for pharmaceutical i

29 that the inhibitory effect of cPLA2alpha on SIRT2 activity impacts various cellular processes, inclu

30 We also directly monitored SIRT1 and SIRT2 activity in HEK293T cells with an mCherry fusion o

31 ry target of sirtinol, and the inhibition of SIRT2 activity may play an important role in cell glucon

32 bulin ultrastructures were resistant against SIRT2 activity.

33 Comparison of the SIRT2 acyl pocket to those of SIRT1, SIRT3, and SIRT6 re

34 hesized and evaluated as novel inhibitors of SIRT2, an enzyme involved in aging-related diseases, e.g

35 Mechanistically, SIRT2, an NAD+-dependent deacetylase, protected neurons

36 of a 1,2,4-oxadiazole analog in complex with Sirt2 and ADP-ribose reveals its orientation in a still

37 d pCAF as RhoGDIalpha-acetyltransferases and Sirt2 and HDAC6 as specific deacetylases, showing the bi

38 tinamides offered excellent activity against SIRT2 and high isozyme selectivity over SIRT1 and SIRT3.

39 that further exploration of the potential of SIRT2 and NAD(+) to delay diseases of aging in mammals i

40 Upon stress, the interaction between SirT2 and PR-Set7 increases along with the H4K20me1 leve

41 5 m(-1) s(-1)), which is the first report of Sirt2 and Sirt6 inhibition by S-nitrosation.

42 The peptide covers both the active site of SIRT2 and the proposed binding site of chroman-4-one-bas

43 ) (acting via deacetylases such as SIRT1 and SIRT2) and succinate (which regulates hypoxia-inducible

44 or SIRT1, 24 with >15.4-fold selectivity for SIRT2, and 8 with 6.8- and 5.3-fold selectivity for SIRT

45 icant selectivity for SIRT6 versus SIRT1 and SIRT2, and are active in cells, as shown by increased ac

46 bitor AGK2, three independent siRNAs against SIRT2, and cells from two independently generated Sirt2-

47 Here we demonstrate that Sirt1, Sirt2, and Sirt3 are expressed in enucleate platelets.

48 The sirtuins SIRT1, SIRT2, and SIRT3 are NAD(+) dependent deacetylases that

49 We found that Sirt1, Sirt2, and Sirt3 can catalyze the hydrolysis of lysine c

50 11c: IC50 = 3.6, 2.7, and 4.0 nM for SIRT1, SIRT2, and SIRT3, respectively).

51 The nuclear Sirt1, the cytosolic Sirt2, and the mitochondrial Sirt3 are robust deacetylas

52 cal mediators such as sAPPalpha:Abeta, SirT1:SirT2, APP:phosphorylated (p)-APP, and Tau:p-Tau, is pro

53 ted factor (PCAF) and deacetylase sirtuin 2 (SIRT2) are responsible for regulating the acetylation st

54 , as well as the primarily cytosolic sirtuin Sirt2, are modified and inhibited by cysteine S-nitrosat

55 Furthermore, we identified a NMT/SIRT2-ARF6 regulatory axis, which may offer new ways to

56 t as well as evaluation of the properties of SIRT2 as a long chain deacylase enzyme.

57 ed effort to explore selective inhibition of SIRT2 as a potential therapy for Parkinson's disease.

58 AziPm and identified the sirtuin deacetylase SIRT2 as a target of the anesthetic.

59 Taken together, these results implicate SIRT2 as an important regulator of programmed necrosis a

60 fied that the protein deacetylase sirtuin 2 (SIRT2) as a novel interactor of LMAN2.

61 he cytoplasmic NAD(+)-dependent deacetylase, Sirt2, as a novel AKT interactor, required for optimal A

62 The NAD-dependent deacetylase sirtuin 2 (SIRT2) associated with and deacetylated K8.

63 Cyclin A-Cdk2 then phosphorylates SIRT2 at Ser331.

64 SirT2 binds and deacetylates PR-Set7 at K90, modulating

65 , we show that the NAD-dependent deacetylase SIRT2 binds constitutively to RIP3 and that deletion or

66 Here we demonstrate that SIRT2 binds, deacetylates, and inhibits the peroxidase a

67 re, genetic or pharmacological inhibition of SIRT2 blocks cellular necrosis induced by TNF-alpha.

68 Remarkably, the loss of SIRT2 blunted the response of AMPK to metformin treatmen

69 SIRT2 bound to LKB1 and deacetylated it at lysine 48, wh

70 Ectopic overexpression of SIRT2, but not its catalytically dead mutant, increased

71 ogether, our data suggest that inhibition of SIRT2 by these compounds causes increased activation of

72 e tumor-permissive phenotype of mice lacking Sirt2 Cancer Res; 76(13); 3802-12.

73 This phosphorylation reduces SIRT2 catalytic activity and its binding affinity to cen

74 of DNA-damage response proteins by impairing SIRT2 catalytic activity or protein levels but not its l

75 idues that line the propofol binding site on SIRT2 contact the sirtuin co-substrate NAD(+) during enz

76 ssive function in which somatic mutations in SIRT2 contribute to genomic instability by impairing its

77 ort, Clta, Stx2, Tjp1, cell survival, Capn3, Sirt2, Csda, sarcomere and cytoskeleton organization and

78 The inhibition of the SIRT2 deacetylase activity by TPPP/p25 is evolved by the

79 SIRT1 and SIRT2 deacetylate FOXO factors to regulate FOXO function

80 for its phosphorylation, whereas Sirtuin 2 (SIRT2) deacetylated MARCKS.

81 of pure samples of alphaTAT1-acetylated and SIRT2-deacetylated microtubules to visualize the structu

82 We found that SIRT2 deacetylates cyclin-dependent kinase 9 (CDK9) in a

83 We demonstrate that SIRT2 deacetylates Foxo3a, activates Bim, and induces ap

84 We show here that SIRT2 deacetylates Foxo3a, increases RNA and protein lev

85 Furthermore, in Mtb specific T cells, SIRT2 deacetylates NFkappaB-p65 at K310 to modulate T he

86 nversely, the protein deacetylase sirtuin 2 (SIRT2) deacetylates and destabilizes ACLY.

87 nzymatic catalysis, and assays that measured SIRT2 deacetylation of acetylated alpha-tubulin revealed

88 ue culture models, we identified a candidate SIRT2 deacetylation target at PKM2 lysine 305 (K305).

89 Pharmacologic or genetic inhibition of SIRT2 decreased K8 solubility and affected filament orga

90 s induction of DNA damage and micronuclei of SIRT2 deficiency in cancer cells.

91 Although Sirt2 deficiency in mice leads to tumorigenesis, the fun

92 SIRT2 deficiency results in replication stress sensitivi

93 he replication stress response impairment of SIRT2 deficiency.

94 acting protein (ATRIP) focus accumulation of SIRT2 deficiency.

95 Accordingly, SirT2-deficient animals exhibit genomic instability and

96 rexpression of a deacetylated PKM2 mutant in Sirt2-deficient mammary tumor cells altered glucose meta

97 This regulatory effect of cPLA2alpha on SIRT2 defines a novel function of cPLA2alpha independent

98 rReal-based PROTAC induced isotype-selective Sirt2 degradation that results in the hyperacetylation o

99 In mice, SIRT2 deletion increased TUG acetylation and proteolytic

100 Finally, we observed that Sirt2 deletion reduced cell viability in response to iro

101 emonstrate that RIP1 is a critical target of SIRT2-dependent deacetylation.

102 eperfusion injury, RIP1 is deacetylated in a SIRT2-dependent fashion.

103 ve stimuli to decrease G6PD acetylation in a SIRT2-dependent manner.

104 on apoptosis, pharmacological inhibition of SIRT2-dependent p53 deacetylation is of great therapeuti

105 es increased activation of p53 by decreasing SIRT2-dependent p53 deacetylation.

106 Here, we have demonstrated that SIRT2 depletion results in a decrease in cellular iron l

107 Consistently, SirT2 depletion significantly reduces PR-Set7 chromatin

108 TPPP/p25 counteracts the SIRT2-derived tubulin deacetylation producing enhanced m

109 in vitro experiments with recombinant human SIRT2 determined that propofol and [(3)H]AziPm only bind

110 with enlarged late endolysosome, knockout of SIRT2 did not exhibit endolysosome enlargement for incre

111 cal inhibition or genetic down-regulation of Sirt2 diminished AKT activation in insulin and growth fa

112 processes require iron, we hypothesized that SIRT2 directly regulates cellular iron homeostasis.

113 We show that SIRT2 directs replication stress responses by regulating

114 Restoring SIRT2 expression in the developing neuroepithelium exert

115 c cocaine administration increases SIRT1 and SIRT2 expression in the mouse NAc, while chronic morphin

116 Loss of SIRT2 expression resulted in exosomal release of LMAN2,

117 ated whether FOXO3 deacetylation by SIRT1 or SIRT2 facilitates FOXO3 ubiquitination and subsequent pr

118 tion that deacetylation of FOXO3 by SIRT1 or SIRT2 facilitates Skp2-mediated FOXO3 poly-ubiquitinatio

119 en together, our results argued that loss of SIRT2 function in cancer cells reprograms their glycolyt

120 obust histone modifications at the Sirt1 and Sirt2 genes.

121 motif-containing 44 [TRIM44], and sirtuin 2 [SIRT2]) had the strongest correlation with long-term sur

122 Similarly, SIRT2 has been demonstrated to be upregulated in some ca

123 The human isotype Sirt2 has been implicated in the pathogenesis of cancer,

124 Second, DNA-bound SerRS recruits the SIRT2 histone deacetylase to erase prior c-Myc-promoted

125 Dysregulation of human Sirt2 (hSirt2) activity has been associated with the pat

126 and AEM2, which are selective inhibitors of SIRT2 (IC50 values of 18.5 and 3.8 muM, respectively), b

127 atios of neuroprotective SirT1 to neurotoxic SirT2; (iii) triggers Tau phosphorylation and APP phosph

128 Herein, we show that SIRT2 impedes the TPPP/p25-promoted microtubule assembly

129 e (PKM2) as a critical target of the sirtuin SIRT2 implicated in cancer.

130 We aimed to investigate the roles of SIRT2 in aging-related and angiotensin II (Ang II)-induc

131 Overexpression of SIRT2 in BubR1(H/H) animals increases median lifespan, w

132 To further establish the role of SIRT2 in cancers, it is necessary to develop selective a

133 The crystal structure of SIRT2 in complex with a thiomyristoyl peptide reveals th

134 present high-resolution structures of human Sirt2 in complex with highly selective drug-like inhibit

135 regimen is prevented by genetic deletion of SIRT2 in mouse.

136 We sought to confirm and explore the role of SIRT2 in necroptosis and tested four different sources o

137 we establish an essential role for SIRT1 and SIRT2 in regulating behavioral responses to cocaine and

138 lectively, our results define a function for SIRT2 in regulating checkpoint pathways that respond to

139 AKT was prebound with Sirt2 in serum or glucose-deprived cells, and the comple

140 Viral-mediated overexpression of SIRT1 or SIRT2 in the NAc enhances the rewarding effects of both

141 results therefore question the importance of SIRT2 in the necroptosis cell death pathway.

142 Furthermore, knockout of SIRT2 increased total number of extracellular vesicles (

143 tional p53, thus establishing a link between SIRT2 inhibition by these compounds and p53 activation.

144 n blot analyses confirmed the involvement of Sirt2 inhibition for their effects in NB4 and in U937 ce

145 he checkpoint protein BubR1, consistent with Sirt2 inhibition in vivo.

146 proliferative effects correlating with their SIRT2 inhibition potency.

147 Mechanistically, SIRT2 inhibition promotes c-Myc ubiquitination and degra

148 for necroptosis based on their findings that SIRT2 inhibition, knock-down or knock-out prevented necr

149 s compound class may be predominantly due to SIRT2 inhibition.

150 We also revealed that a new potent SIRT2 inhibitor (MZ242) and its proteolysis targeting ch

151 netic studies revealed that a representative SIRT2 inhibitor acted competitively against both NAD(+)

152 sis and tested four different sources of the SIRT2 inhibitor AGK2, three independent siRNAs against S

153 ring derived from naphthol, is a dual Sirt1/Sirt2 inhibitor of low potency, whereas EX-527 is a pote

154 at we have discovered a potent and selective SIRT2 inhibitor whose novel structure merits further exp

155 usly, we reported a novel thienopyrimidinone SIRT2 inhibitor with good potency and excellent selectiv

156 ted the anti-diabetic effects of sirtinol, a SIRT2 inhibitor, on cell gluconeogenesis in vivo and in

157 The photoactive diazirine 4, a potent SIRT2 inhibitor, was subjected to detailed photochemical

158 SIRT2 inhibitor-treated mice display reduced bacillary l

159 a nanomolar SIRT1 inhibitor and a micromolar SIRT2 inhibitor.

160 These compounds are potent Sirt2 inhibitors active at single-digit muM level by usi

161 Sirt1 and Sirt2 inhibitors additively inhibited the constitutive A

162 understanding of the mechanism of action of SIRT2 inhibitors and to the identification of refined, s

163 Here we report a series of Sirt2 inhibitors based on the 1,2,4-oxadiazole scaffold.

164 eport novel chroman-4-one and chromone-based SIRT2 inhibitors containing various heterofunctionalitie

165 tes enabling enzyme-economical evaluation of SIRT2 inhibitors in a continuous assay format as well as

166 ts suggest potential usefulness of Sirt1 and Sirt2 inhibitors in the treatment of cancer cells with u

167 ional basis for the development of optimized Sirt2 inhibitors is lacking so far.

168 Therefore, designing SIRT2 inhibitors might be helpful to develop effective t

169 l)oxy)nicotinamides represent a new class of SIRT2 inhibitors that are attractive candidates for furt

170 Herein we report our discovery of novel SIRT2 inhibitors using a fragment-based approach.

171 Our results provide novel Sirt2 inhibitors with a compact scaffold and structural

172 lysine-derived thioureas as mechanism-based SIRT2 inhibitors with anticancer activity.

173 eals) as highly potent and isotype-selective Sirt2 inhibitors with thalidomide, a bona fide cereblon

174 is known about the anti-diabetic activity of SIRT2 inhibitors.

175 interest in the discovery and development of SIRT2 inhibitors.

176 starting point for the development of novel SIRT2 inhibitors.

177 rom our previously reported human sirtuin 2 (SIRT2) inhibitors that were based on a 5-aminonaphthalen

178 gues have been identified with submicromolar SIRT2 inhibtory activity and good to excellent SIRT2 sub

179 SIRT2 interacts with and deacetylates CDK9 at lysine 48

180 SIRT2 is a cytoplasmic sirtuin that plays a role in vari

181 These experiments indicate that sirt2 is a functional mir-92a target and that mir-92a mo

182 SIRT2 is a protein deacetylase with tumor suppressor act

183 SIRT2 is a strong deacetylase that is highly expressed i

184 Sirt2 is a target for the treatment of neurological, met

185 T116 xenograft murine model, supporting that SIRT2 is a viable therapeutic target for colorectal canc

186 tion level of alpha-tubulin, indicating that SIRT2 is likely to be the target in cancer cells.

187 Drug induction of SIRT1 and SIRT2 is mediated in part at the transcriptional level v

188 We also found that SIRT2 is subsequently required for the transcription of

189 Sirtuin 2 (SIRT2) is a protein lysine deacylase that has been indic

190 Sirtuin 2 (SIRT2) is a sirtuin family deacetylase that directs acet

191 Sirtuin 2 (SIRT2) is a sirtuin family deacetylase, which maintains

192 Sirtuin 2 (SIRT2) is an NAD(+)-dependent protein deacetylase whose

193 Sirtuin 2 (SIRT2) is one of the sirtuins, a family of NAD(+)-depend

194 ance tests, glucose disposal was enhanced in SIRT2 knock-out mice, compared with wild type controls,

195 reased acetylation of TIAM1, whereas chronic SIRT2 knockdown resulted in enhanced acetylation of TIAM

196 little impact on endogenous PEPCK1 levels in SIRT2-knockdown cells.

197 Sirt2 knockout markedly exaggerated cardiac hypertrophy

198 200 mg/kg/d) was used to treat wild-type and Sirt2 knockout mice infused with Ang II.

199 Male C57BL/6J wild-type and Sirt2 knockout mice were subjected to the investigation

200 I (1.3 mg/kg/d for 4 weeks) in male C57BL/6J Sirt2 knockout mice, cardiac-specific SIRT2 transgenic (

201 g activated ALDH1A1 through the induction of SIRT2, leading to ALDH1A1 deacetylation and enzymatic ac

202 Deletion of SIRT2 leads to the reduction of apoptosis due to an incr

203 es PDF neuronal excitability via suppressing SIRT2 levels in a rhythmic manner.

204 SirT2 loss in mice induces significant defects associate

205 Mechanistically, SIRT2 maintained the activity of AMP-activated protein k

206 Mechanistically, we determined that SIRT2 maintains cellular iron levels by binding to and d

207 tylation of CDK9, providing insight into how SIRT2 maintains genome integrity and a unique mechanism

208 Thus, SIRT2 may be a novel molecular target for diabetes thera

209 me integrity and a unique mechanism by which SIRT2 may function, at least in part, as a tumor suppres

210 NAMPT/SIRT2-mediated activation of LMO2 by deacetylation appea

211 The SIRT2-mediated deacetylation and activation of G6PD stim

212 We further demonstrate that SIRT2-mediated lysine defatty-acylation promotes endomem

213 bition of NER using spironolactone abolished SIRT2-mediated TC-NER activity in differentiated neurona

214 Furthermore, the hearts of Sirt2(-/-) mice, or wild-type mice treated with a specif

215 Moreover, livers from Sirt2-/- mice had decreased iron levels, while this effe

216 Furthermore, Sirt2-/- mice succumbed to TNF induced Systemic Inflamma

217 , and cells from two independently generated Sirt2-/- mouse strains, however we were unable to show t

218 We observed that these SIRT2 mutant proteins fail to restore the replication st

219 Moreover, the SIRT2 mutant proteins failed to rescue the spontaneous i

220 w that naturally occurring cancer-associated SIRT2 mutations at evolutionarily conserved sites disrup

221 the biological and clinical significance of SIRT2 mutations in genome maintenance and tumor suppress

222 esis, the functional significance of somatic SIRT2 mutations in human tumors is unclear.

223 on levels, while this effect was reversed in Sirt2-/- Nrf2-/- double-KO mice.

224 Sirtuin 2 (SIRT2), one of the mammalian nicotinamide adenine dinucl

225 Overexpression of SIRT2 or treatment of mice with the NAD(+) precursor nic

226 vivo knockdown of the deacetylases HDAC6 and Sirt2, or administration of TSA rescues both axonal tran

227 sized compounds show high selectivity toward SIRT2 over SIRT1 and SIRT3 and represent an important st

228 tivity (48 nM) and excellent selectivity for SIRT2 over SIRT1 and SIRT3.

229 and growth factor-responsive cells, whereas Sirt2 overexpression enhanced the activation of AKT and

230 Conversely, cardiac-specific SIRT2 overexpression protected the hearts against Ang II

231 SIRT2 overexpression reduced TUG acetylation and redistr

232 phosphoribosyltransferase (NAMPT)/sirtuin 2 (SIRT2) pathway.

233 olved a novel AMP-activated kinase-dependent Sirt2 phosphorylation at Thr(101).

234 (+)-dependent tubulin deacetylase sirtuin-2 (SIRT2) play key roles in oligodendrocyte differentiation

235 Here, we demonstrate that SIRT1 and SIRT2 positively regulate the levels of Rac1-GTP and the

236 ex with a thiomyristoyl peptide reveals that SIRT2 possesses a large hydrophobic pocket that can acco

237 nstrate that even the well-known deacetylase SIRT2 possesses efficient activity for the removal of lo

238 uggests that NMT prefers the GTP-bound while SIRT2 prefers the GDP-bound ARF6.

239 ly to RIP3 and that deletion or knockdown of SIRT2 prevents formation of the RIP1-RIP3 complex in mic

240 We found that SIRT1 and SIRT2 promote FOXO3 poly-ubiquitination and degradation.

241 SIRT2 promotes AMPK activation by deacetylating the kina

242 unable to show that inhibiting or depleting SIRT2 protected cells from necroptosis.

243 Here, we demonstrate that SIRT2 protected mice against cisplatin-induced periphera

244 SIRT2 protein expression levels were downregulated in hy

245 n inhibitors, or siRNA knockdown of SIRT1 or SIRT2 proteins, increases MEK1 acetylation and subsequen

246 Loss of SIRT2 reduces AMPK activation, promotes aging-related an

247 Taken together, our study suggests that SIRT2 regulates cargo loading to MVBs and MVB-to-EV flux

248 Here we show that SirT2 regulates H4K20me1 deposition through the deacetyl

249 and may have implications for the impact of SIRT2-related effects on tumorigenesis and age-related d

250 onstrate that the NAD(+)-dependent deacylase SIRT2 removes the myristoyl group, and our evidence sugg

251 uggest that the tumor suppressor activity of SIRT2 requires its ability to restrict the antioxidant a

252 AziPm photolabeled three SIRT2 residues (Tyr(139), Phe(190), and Met(206)) that a

253 -fold selectivity for SIRT3 versus SIRT1 and SIRT2, respectively.

254 ctly acetylated by KAT7, and deacetylated by Sirt2, respectively.

255 Pharmacological inhibition of SIRT2 restricts the intracellular growth of both drug-se

256 Transient inhibition of SIRT1 and SIRT2 resulted in increased acetylation of TIAM1, wherea

257 rsely, antisense RNA-mediated attenuation of SIRT2 reversed ROS-induced toxicity as demonstrated in a

258 sirt2 RNAi also phenocopies mir-92a overexpression.

259 age promotes RRM2 deacetylation by enhancing Sirt2-RRM2 interaction.

260 Taken together, our results identified SIRT2's function in the NER pathway as a key underlying

261 Importantly, SIRT2's protective effects were not evident in lung canc

262 Our findings support a model for SIRT2's tumor-suppressive function in which somatic muta

263 rectal carcinoma CSCs, while 4b, 6a, and the SIRT2-selective inhibitor AGK-2 showed the highest effec

264 Our studies demonstrate that SIRT2-selective inhibitors are promising anticancer agen

265 tify the binding site of chroman-4-one-based SIRT2-selective inhibitors.

266 The compounds retained both high SIRT2 selectivity and potent inhibitory activity.

267 Potency and the unprecedented Sirt2 selectivity are based on a ligand-induced structur

268 In addition, elevated levels of SIRT2 sensitized breast cancer cells to arsenic trioxide

269 Elevated levels of SIRT2 sensitized breast cancer cells to intracellular DN

270 with a specific pharmacological inhibitor of SIRT2, show marked protection from ischaemic injury.

271 to various human sirtuins, including SIRT1, SIRT2, SIRT3 and SIRT5.

272 as efficient decrotonylases, and that SIRT1, SIRT2, SIRT3, and SIRT4 can remove lipoic acid.

273 e histone deacetylase sirtuin family (SIRT1, SIRT2, SIRT3, SIRT5 and SIRT6) using both recombinant en

274 and inhibit the deacylase activity of Sirt1, Sirt2, Sirt3, Sirt5, and Sirt6.

275 s novel mdx biomarkers (GITR, MYBPC1, HSP60, SIRT2, SMAD3, CNTN1).

276 In contrast to SIRT2, specific binding of [(3)H]AziPm or propofol to re

277 iomyristoyl lysine compound, TM, as a potent SIRT2-specific inhibitor with a broad anticancer effect

278 ctive at single-digit muM level by using the Sirt2 substrate alpha-tubulin-acetylLys40 peptide and in

279 n level of alpha-tubulin, a well-established SIRT2 substrate, in both concentration- and time-depende

280 RT2 inhibtory activity and good to excellent SIRT2 subtype-selectivity.

281 fficient in vitro demyristoylase activity of SIRT2 suggests that this activity may be physiologically

282 Consistent with this, inhibition of NAMPT or SIRT2 suppressed the in vitro growth and in vivo engraft

283 out mice, cardiac-specific SIRT2 transgenic (SIRT2-Tg) mice, and their respective littermates (8 to a

284 cancer cells have an increased dependency on SIRT2 that can be exploited for therapeutic benefit.

285 arker panel, consisting of EGFR, TRIM44, and SIRT2, that is independently associated with OS and prov

286 y of uncoupling protein-2 (UCP2), sirtuin-2 (SIRT2), the G protein-coupled receptor GPR109A or hydroc

287 propofol inhibits the mammalian deacetylase SIRT2 through a conformation-specific, allosteric protei

288 bridge in this complex to promote binding of SIRT2 to cyclin A-Cdk2.

289 ue to a decline in NAD(+) and the ability of SIRT2 to maintain lysine-668 of BubR1 in a deacetylated

290 Co-localization of the SIRT2-TPPP/p25 complex on the microtubule network was vi

291 7BL/6J Sirt2 knockout mice, cardiac-specific SIRT2 transgenic (SIRT2-Tg) mice, and their respective l

292 The most potent inhibitor of SIRT2 was 6,8-dibromo-2-pentylchroman-4-one with an IC(5

293 Recently Narayan et al., reported that SIRT2 was required for necroptosis based on their findin

294 Novel enzymatic activities of SIRT2 were thus established in vitro, which warrant furt

295 AD+ dependent histone deacetylase Sirtuin 2 (SIRT2), which upon infection translocate to the nucleus

296 dicate that mir-92a suppresses expression of sirt2, which is homologous to human sir2 and sirt3.

297 Sirt2, which level peak in S phase, sustains RNR activit

298 These findings indicate that SIRT2 will be a potential target for therapeutic interve

299 ds AF8, AF10, and AF12 selectively inhibited SIRT2 with IC(50) values of 0.06, 0.15, and 0.08 muM, re

300 nol (IC50 approximately 50 muM for SIRT1 and SIRT2) with in vitro and in vivo antilymphoma activity.