ライフサイエンスコーパス: SIRT2

1 h good potency and excellent selectivity for SIRT2.

2 th Golgi matrix proteins and is regulated by SIRT2.

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

4 trol of the sirtuin family members SIRT1 and SIRT2.

5 he class III histone deacetylases, SIRT1 and SIRT2.

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

7 mechanism mediated redundantly by Sirt1 and Sirt2.

8 on from Sirt1 and increased association with Sirt2.

9 es act as potent and selective inhibitors of SIRT2.

10 ted upon hyperglycemia and down-regulated by SIRT2.

11 ide revealed that WIF-B cells do not express SirT2.

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

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

14 find that a previously uncharacterized form, SIRT2.3, exhibits age-dependent accumulation in the mous

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

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

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

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

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

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

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

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

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

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

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

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

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

28 bulin ultrastructures were resistant against SIRT2 activity.

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

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

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

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

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

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

35 regulated through reversible acetylation by SIRT2 and p300.

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

37 me members of this group of proteins (SirT1, SirT2 and SirT3) and deacetylation of a specific residue

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

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

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

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

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

43 ylated alpha-tubulin, a primary substrate of SirT2, and MAP2c, both of which are linked to increased

44 etyl-CoA synthetase-1; measurement of Sirt1, Sirt2, and Sirt3 activities from mammalian cell extracts

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

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

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

48 11c: IC50 = 3.6, 2.7, and 4.0 nM for SIRT1, SIRT2, and SIRT3, respectively).

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

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

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

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

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

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

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

56 (+)-dependent deacetylase Sir-two-homolog 2 (Sirt2) as a protein likely to be involved in myelination

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

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

59 Cyclin A-Cdk2 then phosphorylates SIRT2 at Ser331.

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

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

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

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

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

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

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

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

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

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

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

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

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

73 These results demonstrate that Sirt2 controls an essential polarity pathway in SCs duri

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

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

76 SIRT1 and SIRT2 deacetylate FOXO factors to regulate FOXO function

77 whereas Drosophila Sir2 and human SIRT1 and SIRT2 deacetylate H3K56ac.

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

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

80 SIRT2 deacetylates lysine residues in the catalytic doma

81 hat the NAD(+)-dependent histone deacetylase SIRT2 deacetylates p300 in vitro and in cells.

82 In SCs, we found that Sirt2 deacetylates Par-3, a master regulator of cell pol

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

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

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

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

87 The deacetylation of Par-3 by Sirt2 decreases the activity of the polarity complex sig

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

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

90 SIRT2 deficiency results in replication stress sensitivi

91 he replication stress response impairment of SIRT2 deficiency.

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

93 Accordingly, SirT2-deficient animals exhibit genomic instability and

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

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

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

97 In mice, SIRT2 deletion increased TUG acetylation and proteolytic

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

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

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

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

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

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

104 The altered ac-p300/p300 ratio in SIRT2-depleted cells results in decreased p300 recruitme

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

106 Consistently, SirT2 depletion significantly reduces PR-Set7 chromatin

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

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

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

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

111 We show that SIRT2 directs replication stress responses by regulating

112 tudies reveal that focal areas of endogenous SIRT2 expression correlate with reduced alpha-tubulin ac

113 Additionally, cold exposure elevates SIRT2 expression in brown adipose tissue but not in whit

114 Here, we show that Sirt2 expression in SCs is correlated with that of struc

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

116 -adrenergic agonist (isoproterenol) enhances SIRT2 expression in white adipose tissue.

117 m food deprivation for 24 h, already induces SIRT2 expression in white and brown adipose tissues.

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

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

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

121 obust histone modifications at the Sirt1 and Sirt2 genes.

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

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

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

125 In non-neuronal cells, SIRT2 has been shown to function as a tubulin deacetylas

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

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

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

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

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

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

132 Retroviral expression of SIRT2 in 3T3-L1 adipocytes promotes lipolysis.

133 tasis, we went on to explore the function of SIRT2 in adipose tissue.

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

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

136 mediated depletion or chemical inhibition of SIRT2 in cells results in accumulation of acetylated p30

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

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

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

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

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

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

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

144 ferential expression of specific isoforms of SIRT2 in the mammalian central nervous system and find t

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

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

147 istone deacetylase 6 (HDAC6) and Sirtuin T2 (SirT2), in WIF-B cells.

148 sion of one of the seven mammalian sirtuins, SIRT2, in tissues such as white adipose tissue.

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

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

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

152 proliferative effects correlating with their SIRT2 inhibition potency.

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

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

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

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

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

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

159 luorescence microscopy, and assays using the SirT2 inhibitor nicotinamide revealed that WIF-B cells d

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

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

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

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

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

165 de dimer 3, the latter a novel and selective SIRT2 inhibitor, were isolated from the Madagascar marin

166 a nanomolar SIRT1 inhibitor and a micromolar SIRT2 inhibitor.

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

168 Sirt1 and Sirt2 inhibitors additively inhibited the constitutive A

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

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

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

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

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

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

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

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

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

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

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

180 interest in the discovery and development of SIRT2 inhibitors.

181 starting point for the development of novel SIRT2 inhibitors.

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

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

184 SIRT2 inhibits 3T3-L1 adipocyte differentiation in low-g

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

186 SIRT2 interacts with and deacetylates CDK9 at lysine 48

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

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

189 SIRT2 is a protein deacetylase with tumor suppressor act

190 SIRT2 is a strong deacetylase that is highly expressed i

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

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

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

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

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

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

197 Sirtuin 2 (SIRT2) is one of seven known mammalian protein deacetyla

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

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

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

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

202 Sirt2 knockout markedly exaggerated cardiac hypertrophy

203 200 mg/kg/d) was used to treat wild-type and Sirt2 knockout mice infused with Ang II.

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

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

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

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

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

209 SirT2 loss in mice induces significant defects associate

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

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

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

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

214 d suggest that the brain-enriched species of SIRT2 may function as the predominant MT deacetylases in

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

216 The SIRT2-mediated deacetylation and activation of G6PD stim

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

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

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

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

221 owever, the distribution and function of the SIRT2 microtubule (MT) deacetylase in differentiated, po

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

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

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

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

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

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

228 ts showing age-dependent accumulation of the SIRT2 neuronal MT deacetylase in wild-type mice suggest

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

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

231 nhibited by expressing exogenous deacetylase SIRT2 or HDAC6.

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

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

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

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

236 inhibitors and show isoform selectivity for SIRT2 over SIRT1.

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

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

239 SIRT2 overexpression reduced TUG acetylation and redistr

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

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

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

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

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

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

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

247 SIRT2 promotes AMPK activation by deacetylating the kina

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

249 SIRT2 protein expression levels were downregulated in hy

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

251 pharmacological reduction of either Sir2 or Sirt2 provides neuroprotection to Htt-challenged animals

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

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

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

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

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

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

258 Overall, our results indicate that SIRT2 responds to nutrient deprivation and energy expend

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

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

261 sirt2 RNAi also phenocopies mir-92a overexpression.

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

263 lls was also observed for both a SIRT1 and a SIRT2 selective analog.

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

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

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

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

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

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

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

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

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

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

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

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

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

277 Transgenic mice lacking or overexpressing Sirt2 specifically in SCs show delays in myelin formatio

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 Mechanistically, SIRT2 suppresses adipogenesis by deacetylating FOXO1 to

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 Genetic inhibition of SIRT2 via small interfering RNA similarly rescued alpha-

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

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

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

296 including a new role for sirtuins (Sirt1 and Sirt2)-which are induced in the nucleus accumbens by coc

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

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

299 Tanikolide dimer 3 (= 5) inhibited SIRT2 with an IC(50) = 176 nM in one assay format and 2.

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