ライフサイエンスコーパス: NPM

1 NPM and AurA coimmunoprecipitate and colocalize to centr

2 NPM enhances the expression of p53 target gene p21 and b

3 NPM induces phosphorylation of AurA on serine 89, and th

4 NPM is a potential cotarget in combination with other th

5 NPM is an endogenous inhibitor of HDM2:p53 interaction a

6 NPM is translationally responsive to hyperactive mammali

7 NPM knockdown reduces heat-induced inhibition of DNA DSB

8 NPM mRNA destabilization involves the association of HuR

9 NPM-ALK acts through STAT3, a transcription factor that

10 NPM-ALK co-opts several intracellular signal transductio

11 NPM-ALK induces ICOS expression via STAT3, which trigger

12 NPM-ALK is a chimeric tyrosine kinase, which induces num

13 NPM-ALK L182M, L182V, and L256M mutants displayed kinase

14 NPM-ALK-deregulated kinase activity drives several pathw

15 NPM-Bax complex formation is a novel target for preventi

16 NPM/ALK induces HIF1alpha expression by upregulating its

17 NPM/B23 phosphorylated by CDK2-cyclin E acquires a high

18 te catalyst, [Ru(II)(NPM)(4-pic)2(H2O)](2+) (NPM = 4-t-butyl-2,6-di(1',8'-naphthyrid-2'-yl)pyridine,

19 The rate constant derived for the O(3)-NPM reaction is 1 x 10(-18) cm(3).s(-1), and the diffusi

20 poptosis inhibition (CASP-9, CASP-7, DFF-45, NPM, YWHAZ, Src, PAX2, MAPK8), cell cycle promotion and

21 ndence by ectopic expression of an activated NPM-ALK fusion oncoprotein.

22 mitochondrial translocation and activation, NPM helps human HCC cells evade death induction independ

23 th previously characterized AurA activators, NPM does not trigger autophosphorylation of AurA on thre

24 In addition, NPM is necessary for the ability of c-Myc to induce rRNA

25 In addition, NPM-ALK uses epigenetic silencing mechanisms to downregu

26 mphoma kinase (ALK), with nucleophosmin-ALK (NPM-ALK) fusions being the most common.

27 cumulative incidence rates of developing an NPM after stage III melanoma were 1.2% (95% CI, 0.86% to

28 achieved substantial tumor regression in an NPM-ALK driven murine tumor xenograft model when dosed q

29 ways identified as affected by both IL-2 and NPM/ALK.

30 e compared samples of primary NPM-ALK(+) and NPM-ALK(-) ALCL to investigate the role of miR-150 downs

31 hematopoietic precursor differentiation and NPM-ALK+ cell growth.

32 Targeting the interaction between FOXM1 and NPM by peptides or small molecules may represent a novel

33 confirmed the interaction between FOXM1 and NPM in cancer and immortal cells.

34 t understanding of the biology of IGF-IR and NPM-ALK and have significant therapeutic implications as

35 l functional interactions between IGF-IR and NPM-ALK.

36 The dynamic behavior of NS and NPM reveal that nucleolar disruption is an early event a

37 Rapid translocation of NS and NPM to the nucleoplasm and suppression of new preribosom

38 ed protein binding, including La, P54nrb and NPM.

39 uch as TEL/ABL, TEL/JAK2, TEL/PDGFbetaR, and NPM/ALK also elevate WRN.

40 the NPM-ALK is not active and sequestered as NPM-ALK/NPM1 heterodimers in the nucleus.

41 Nucleophosmin/B23 (NPM) is a pleiotropic nucleolar protein involved in a va

42 e growth inhibition and cytotoxicity of BaF3/NPM-ALK mutant cells induced by ALK inhibitors were cons

43 indings are of clinical significance because NPM up-regulation and p53 mutations are usually found in

44 (CDK1, CDK2, CDK8, CHEK1, CHEK2, GSK-3 beta, NPM, PAK1, PP2C-alpha).

45 tation revealed a direct interaction between NPM and BAX in the cytoplasm.

46 our previous finding that ARF directly binds NPM, impeding its transit to the cytoplasm and arresting

47 cytosol, NPM-Bax complexes formed, and both NPM and Bax accumulated in mitochondria.

48 thylation is induced in malignant T cells by NPM-ALK.

49 e affected genes were modulated in common by NPM/ALK and IL-2.

50 elocalization of NPM-ALK to the cytoplasm by NPM genetic knockout or knockdown caused ERK1/2 (extrace

51 Phosphorylation of pS(9)-GSK3beta by NPM-ALK was mediated by the PI3K/AKT signaling pathway.

52 ene amplification and is further mediated by NPM-ALK through activation of PI3K/AKT and stabilization

53 Many genes and proteins modulated by NPM-ALK are also involved in evasion of antitumor immune

54 Suppression of NPM by NPM small interfering RNA leads to an increase of p53 le

55 novel actin signaling pathways regulated by NPM-ALK, a comprehensive phosphoproteome analysis of ALC

56 ch syndrome protein (WASp) were regulated by NPM-ALK.

57 tic option in cells that become resistant by NPM-ALK amplification.

58 beta-rearrangement, which is bypassed in CD4/NPM-ALK transgenic mice following Notch1 expression.

59 Cdk2 or Cdk4, we conclude that the Cdk2/Cdk4/NPM pathway is a major guardian of centrosome dysfunctio

60 Our data suggest that in cancer cells NPM interacts with FOXM1 and their interaction is requir

61 were consistent with inhibition of cellular NPM-ALK autophosphorylation.

62 Constitutive expression of the chimeric NPM/ALK fusion protein encoded by the t(2;5)(p32;q35) is

63 We also compared NPM-ALK/ beta-actin ratios determined by ELISA to those

64 synthesis in the nucleolus, and constitutive NPM overexpression stimulates c-Myc-mediated rRNA synthe

65 nucleolar NPM translocated into the cytosol, NPM-Bax complexes formed, and both NPM and Bax accumulat

66 in per cell; based on our in-house developed NPM-ALK ELISA; LOD of 40 pM) as compared to the ubiquito

67 nd a therapeutic target.Methods Differential NPM phosphorylation was assessed by mass spectrometry in

68 A Bax peptide that disrupts NPM-Bax interaction significantly reduced cell death cau

69 by the NPM/ALK fusion, we identified diverse NPM/ALK-induced changes affecting cell proliferation, ri

70 e value of Flt-3 internal tandem duplication/NPM-1 status, with inferior survival seen in patients wi

71 , in a clean cell system in which endogenous NPM had been removed by RNA interference.

72 Also, we found that NS can enhance NPM stabilization of ARF.

73 rfere with NPM function were used to explore NPM as a therapeutic target.Results Within hours of stre

74 nhibited in T-cell lymphoma cells expressing NPM-ALK kinase as a result of DNA methylation of the IL-

75 orylation of NPM-Thr198 is not essential for NPM's capacity to drive cell cycle progression and proli

76 estigate the cell's presumed requirement for NPM-Thr198 phosphorylation in promoting the processes of

77 se results demonstrate an essential role for NPM in c-Myc nucleolar localization and c-Myc-mediated r

78 urt-Munster-type protocols were screened for NPM-ALK transcripts at diagnosis; 103 were found to be M

79 Some of these proteins such as CALR, GRP78, NPM, Hsp27, PDI, ATP synthase subunit alpha, PRDX1, and

80 On the other hand, NPM-ALK L256M exhibited >30-fold lower sensitivity to bo

81 d to cytoplasm in cells with relatively high NPM level, or accumulated in the mitochondria in cells w

82 whereas nontransgenic littermates and hMRP8-NPM transgenic mice remained disease free.

83 milar wild-type NPM trans-genic model (hMRP8-NPM).

84 leukemia was found in hMPR8-NPMc(+) or hMRP8-NPM mice.

85 in E. coli, purified and characterized human NPM-ALK fusion protein to be used as a standard for esti

86 Remarkably, human NPM-ALK-amplified cell lines resistant to ALK tyrosine k

87 Previous studies have shown that the human NPM's phosphorylation by cyclin E-cyclin-dependent kinas

88 f the Ru-based single site catalyst, [Ru(II)(NPM)(4-pic)2(H2O)](2+) (NPM = 4-t-butyl-2,6-di(1',8'-nap

89 NPM ligand modification results in [Ru(III)(NPM-NO)(4-pic)2(H2O)](3+) and [Ru(III)(NPM-NO,NO)(4-pic)

90 (III)(NPM-NO)(4-pic)2(H2O)](3+) and [Ru(III)(NPM-NO,NO)(4-pic)2](3+) complexes.

91 Importantly, NPM-ALK is capable of transforming primary human CD4(+)

92 In NPM-ALK(+) cell lines, DNA hypermethylation-mediated miR

93 he MIR150 gene was substantially elevated in NPM-ALK(+) biopsies and correlated with reduced miR-150

94 letion of FBP1 caused a dramatic increase in NPM translation and resulted in enhanced overall cell pr

95 Early evaluation of MRD in NPM-ALK-positive ALCL identifies patients with a very hi

96 Thus, we demonstrate that the reduction in NPM protein expression blocks cellular growth and prolif

97 tected at distinct serine/threonine sites in NPM harvested from primary renal cells, tissue, and urin

98 ylation was assessed by mass spectrometry in NPM harvested from murine and human primary renal epithe

99 d with wild-type NPM/ALK and kinase-inactive NPM/ALK K210R mutant and by the inhibition of the NPM/AL

100 t a nucleus-restricted NPM mutant, increased NPM-Bax complex formation, mitochondrial NPM and Bax acc

101 on of HuR stabilizes the NPM mRNA, increases NPM protein levels and inhibits myogenesis, while its ov

102 PPAN depletion induces NPM and upstream-binding factor (UBF) degradation, which

103 we hypothesized that ARF might also inhibit NPM phosphorylation.

104 bic SN-38 was successfully encapsulated into NPM with significantly increased water solubility (up to

105 monstrate that the oncogenic tyrosine kinase NPM-ALK induces epigenetic silencing of the IL-2Rgamma g

106 se nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) expressing anaplastic large cell lymphoma are n

107 ound that in ALK-rearranged ALCL cell lines, NPM-ALK was distributed in equal amounts between the cyt

108 he mitochondria in cells with relatively low NPM level and undergoing apoptosis.

109 ssue and used quantitative RT-PCR to measure NPM-ALK fusion transcript in bone marrow and blood sampl

110 A family of mesoporous nonprecious metal (NPM) catalysts for oxygen reduction reaction (ORR) in ac

111 ue class of photonic nanoporphyrin micelles (NPM), the extremely hydrophobic SN-38 was successfully e

112 sed NPM-Bax complex formation, mitochondrial NPM and Bax accumulation, mitochondrial membrane injury,

113 y and hydrophobicity of the nonpolar moiety (NPM) of the anions.

114 The multiple NPM/ALK-deregulated pathways identified by MS analysis a

115 ylation of the cdk2 target residue in murine NPM, Thr198.

116 In murine NPM-ALK(+) xenograft models, miR-150 upregulation induce

117 compared with kinase-defective K210R mutant NPM-ALK, but did not affect total GSK3beta levels.

118 Transfection of wild-type or mutant NPM-ALK into 293T cells showed that only wild-type NPM-A

119 ion, in OCI/AML3 leukemia cells where mutant NPM is localized in the cytoplasm we found that typicall

120 pression of a cytosol-restricted NPM mutant (NPM-DeltaNLS), but not a nucleus-restricted NPM mutant,

121 The neonicotinoid nitenpyram (NPM) is a multifunctional nitroenamine [(R(1)N)(R(2)N)C=

122 s that either mimic stress-induced or normal NPM phosphorylation.

123 Here we report the identification of a novel NPM-BCL2-associated X protein (BAX) pathway orchestratin

124 During stress, nucleolar NPM translocated into the cytosol, NPM-Bax complexes for

125 Nucleophosmin (NPM), a predominantly nucleolar protein, is also critica

126 Nucleophosmin (NPM), an oligomeric phosphoprotein and nucleolar target

127 Nucleophosmin (NPM/B23) is a multifunctional oncoprotein whose protein

128 Nucleophosmin (NPM/B23) is one of the phosphorylation targets of CDK2-c

129 interaction between DDX5 and nucleophosmin (NPM), preventing association of DDX5 with the rDNA promo

130 es, primary human tumours and nucleophosmin (NPM)-ALK-induced murine tumours demonstrate the TPC freq

131 s centrosome duplication, and nucleophosmin (NPM/B23) is found to be one of its targets.

132 harbor the well-characterized nucleophosmin (NPM)-ALK fusion protein.

133 Differential nucleophosmin (NPM) phosphorylation is a potential early marker of isch

134 1 and its downstream effector nucleophosmin (NPM) to rDNA.

135 e chain reaction (RT-PCR) for Nucleophosmin (NPM)-ALK during treatment identifies patients at the hig

136 cells by hyperphosphorylating nucleophosmin (NPM) at Thr199, as evidenced by observations that ablati

137 Recently, we identified nucleophosmin (NPM) as a key factor counteracting death stimuli in huma

138 ently mutated genes in AML is nucleophosmin (NPM), and this is associated with low CD34 expression.

139 Moreover, nucleophosmin (NPM) and c-Myc, both of which are commonly overexpressed

140 y, we report that activity of nucleophosmin (NPM)/ALK chimeric protein, the dominant form of ALK expr

141 cal and functional partner of nucleophosmin (NPM/B23), a major nucleolar phosphoprotein with diverse

142 on of the cell cycle promoter nucleophosmin (NPM).

143 of the anti-apoptotic protein nucleophosmin (NPM).

144 We hypothesized that nucleophosmin (NPM), a nucleolar phosphoprotein, is critical for Bax-me

145 ma Kinase (ALK) gene with the Nucleophosmin (NPM) gene.

146 homa (TCL) cells carrying the nucleophosmin (NPM)/ALK fusion protein (ALK+ TCL) strongly express hypo

147 ic lymphoma kinase (ALK) with nucleophosmin (NPM) and the subsequent expression of the NPM-ALK fusion

148 NS interacts with nucleophosmin (NPM), a marker of nucleolar stress with cytoprotective p

149 with Mdm2, or separately with nucleophosmin (NPM, B23) that localizes and stabilizes p19(Arf) within

150 through its interaction with nucleophosmin (NPM/B23), RNA helicase DDX5 and RNA polymerase I transcr

151 ues as a fusion protein with nucleophosphin (NPM) and other partners.

152 was performed in the presence or absence of NPM-ALK activity.

153 on the expression and enzymatic activity of NPM-ALK.

154 on the expression and enzymatic activity of NPM/ALK, as shown in BaF3 cells transfected with wild-ty

155 L2 was found to result in reduced binding of NPM to HDM2, with concomitant defects in p53 accumulatio

156 Coexpression of NPM-DeltaNLS with constitutively active Bax mutants caus

157 ed loss of cell adhesion as a consequence of NPM/ALK expression in a kinase-dependent manner, and sen

158 phoproteomic and metabolomic consequences of NPM-ALK expression and reveals a novel role of ALK in th

159 data were confirmed in vivo, as depletion of NPM by ribonucleic acid interference eliminated phosphor

160 ve studies evaluated the serial detection of NPM-ALK fusion transcripts in patients with ALCL.

161 nvestigate the role of miR-150 downstream of NPM-ALK.

162 r-expression of FOXM1 reversed the effect of NPM knockdown in vitro.

163 The suppressive effect of NPM on p53 mitochondrial localization is also observed i

164 t contributes to the lymphomagenic effect of NPM-ALK.

165 sis also predicted novel biologic effects of NPM/ALK expression.

166 r, these findings indicate that an excess of NPM-ALK activation and signaling induces apoptosis via o

167 Expression of NPM enhances p53 levels in the nucleus but reduces p53 l

168 Expression of NPM-ALK in 293T cells led to an increase of pS(9)-GSK3be

169 cation, leading to the ectopic expression of NPM-ALK, a chimeric tyrosine kinase.

170 sor by reciprocally inhibiting expression of NPM-ALK.

171 e show that oxidation of thin solid films of NPM by gas-phase ozone produces unexpected products, the

172 Since a mutant form of NPM lacking the G(1) Cdk phosphorylation site (NPM(T199A

173 ediates the phosphorylation of a fraction of NPM at threonine 199, an event required for its proteaso

174 ng Western blotting and/or immunostaining of NPM/ALK-transfected cells and ALK-deregulated lymphomas.

175 Implantation of NPM-ALK-transformed CD4(+) T lymphocytes into immunodefi

176 Implantation of NPM-ALK-transformed CD4+ T lymphocytes into immunodefici

177 multiple primaries had a higher incidence of NPM.

178 clinical studies indicate that inhibition of NPM-ALK induces long-lasting complete remissions in a la

179 Furthermore, knockdown of NPM in immortal and cancer cells led to significant down

180 Levels of NPM-ALK decreased during therapy in most patients with A

181 rt for the role of GSK3beta as a mediator of NPM-ALK oncogenesis.

182 entified GSK3beta as a signaling mediator of NPM-ALK.

183 nd proliferation, whereas phosphorylation of NPM-Thr198 is not essential for NPM's capacity to drive

184 entify a novel cell-transforming property of NPM/ALK, namely its ability to induce the expression of

185 th, and 1-year cumulative incidence rates of NPM after diagnosis of stage IV melanoma were 0.2% (95%

186 Reduction of NPM significantly reduces heat-induced radiosensitizatio

187 Clinically, up-regulation of NPM was significantly associated with advanced tumor sta

188 Overexpression or relocalization of NPM-ALK to the cytoplasm by NPM genetic knockout or knoc

189 FBP1 resulted in translational repression of NPM mRNAs, whereas depletion of FBP1 caused a dramatic i

190 kinase-dependent manner, and sensitivity of NPM/ALK-positive ALCLs to inhibition of the RAS, p42/44E

191 s kinase in the topological sequestration of NPM, linking p53 signaling to the generation of threonin

192 lar fractionation revealed that silencing of NPM expression greatly enhanced mitochondrial translocat

193 Silencing of NPM expression significantly sensitized HCC cells-partic

194 sensitization effect exerted by silencing of NPM in HCC cells.

195 Silencing of NPM significantly sensitized HCC cells to anticancer the

196 on of STAT3, a major downstream substrate of NPM-ALK, in cooperation with DNA methyltransferase 1 (DN

197 Suppression of NPM by NPM small interfering RNA leads to an increase of

198 n cells comparable to or higher than that of NPM-ALK wild type (WT) and rendered BaF3 cells into IL-3

199 -derived ALK inhibitor comparable to that of NPM-ALK WT but were dramatically less sensitive to a dia

200 The biologic behavior and toxicity of NPM was assessed using phospho-NPM mutant proteins that

201 1) interacts specifically with the 3' UTR of NPM to repress translation.

202 The expression dependence on NPM/ALK and IL-2 of the five selected genes-CD25 (IL-2Ra

203 ue features, which are strictly dependent on NPM-ALK activity and expression, include perpetual cell

204 ion, and survival were strictly dependent on NPM-ALK activity and include activation of the key facto

205 ;q35), which generates the chimeric oncogene NPM-ALK.

206 ents with stage IV melanoma had at least one NPM after diagnosis of stage III or IV disease.

207 stress, whereas expression of active Bax or NPM-DeltaNLS alone did not.

208 Knockdown of FOXM1 or NPM in MIA PaCa-2 pancreatic cancer cells inhibited anch

209 Overexpression of either NS or NPM significantly decreases caspase 8 activity in cultur

210 d toxicity of NPM was assessed using phospho-NPM mutant proteins that either mimic stress-induced or

211 A phosphomimic NPM protein that replicated phosphorylation under stress

212 fter stress; wild-type NPM or a phosphomimic NPM with a normal phosphorylation configuration did not.

213 amined the effects of a non-phosphorylatable NPM mutant, T198A, in a clean cell system in which endog

214 e generation of threonine 199-phosphorylated NPM.

215 d for the translocation of de-phosphorylated NPM from the nucleolus to the nucleoplasm.

216 ions These findings establish phosphorylated NPM as a potential early marker of ischemic AKI that lin

217 The Thr199-phosphorylated NPM/B23 physically interacts with and super-activates th

218 phosmin-anaplastic lymphoma kinase-positive (NPM-ALK(+)) anaplastic large-cell lymphoma (ALCL) as mod

219 olar stress-response pathway involving PPAN, NPM, and BAX to guarantee cell survival in a p53-indepen

220 Rac1 single deletions, completely prevented NPM-ALK lymphoma dissemination in vivo.

221 K-transformed CD4+ T lymphocytes and primary NPM-ALK+ ALCL biopsies share similarities with early T c

222 Here, we compared samples of primary NPM-ALK(+) and NPM-ALK(-) ALCL to investigate the role o

223 We transplanted sorted fractions of primary NPM-mutated AML into immunodeficient mice to establish w

224 5; p23;q35) that produces the fusion protein NPM-ALK (nucleophosmin-anaplastic lymphoma kinase).

225 ncers interacts with multifunctional protein NPM, which is also overexpressed in a variety of human t

226 ported to the North Pacific margin province (NPM) by East Asian winter monsoon.

227 s rRNA synthesis through a PKCiota-Ect2-Rac1-NPM signaling axis that is required for lung tumorigenes

228 heat-induced radiosensitization, but reduced NPM level does not alter radiation sensitivity per se.

229 selectively bind the NPM 3' UTR and repress NPM translation.

230 Treatment of crizotinib-resistant NPM-ALK(+) KARPAS-299-CR06 cells with decitabine or ecto

231 With regard to inhibitor response, NPM-ALK L182M and L182V exhibited sensitivity to a fused

232 Expression of a cytosol-restricted NPM mutant (NPM-DeltaNLS), but not a nucleus-restricted

233 (NPM-DeltaNLS), but not a nucleus-restricted NPM mutant, increased NPM-Bax complex formation, mitocho

234 M lacking the G(1) Cdk phosphorylation site (NPM(T199A)) prevents centrosome amplification to the sam

235 N-38-encapsulated nanoporphyrin micelles (SN-NPM) enhanced the in vitro antitumor activity by 78 and

236 Due to the relatively small size, SN-NPM possessed superior long tumor retention time (>5days

237 l-, photodynamic- and chemo-therapy) with SN-NPM demonstrated dramatically enhanced in vivo antitumor

238 degradation and maintenance of steady-state NPM levels.

239 Following cell stress, NPM and BAX were induced and exported out of the nucleol

240 another rationale to therapeutically target NPM/ALK and STAT3 in ALK+ TCL.

241 Our data demonstrate that NPM is a strong activator of AurA kinase activity at the

242 Our results demonstrate that NPM-ALK regulates the phosphorylation of S(9)-GSK3beta b

243 These results demonstrate that NPM-ALK, acting through STAT3 as the gene transcriptiona

244 Previously, we demonstrated that NPM directly interacts with c-Myc and controls c-Myc-ind

245 rase pull-down experiments demonstrated that NPM forms a complex with FOXM1 and also identified the r

246 We estimated that NPM-ALK fusion protein is expressed at substantial level

247 It has been found that NPM/B23 phosphorylated on Thr199 by CDK2-cyclin E acquir

248 These findings indicate that NPM/ALK transforms the target CD4(+) T lymphocytes, at l

249 In the present study, we report that NPM is a strong activator of AurA kinase activity.

250 Integration of "Omic" data revealed that NPM-ALK-transformed CD4+ T lymphocytes and primary NPM-A

251 Here, we show that NPM is necessary for the localization of c-Myc protein t

252 Here we show that NPM-ALK phosphorylates WASp at its known activation site

253 osphoproteomic and metabolomic strategy that NPM-ALK induces a metabolic shift toward aerobic glycoly

254 Also, these results suggest that NPM associates with nuclear matrix attachment region DNA

255 in stress-induced apoptosis and suggest that NPM may protect cells from apoptosis by reducing the mit

256 for the first time our findings suggest that NPM-ALK could restore progenitor-like features in mature

257 of FOXM1 from the cytoplasm, suggesting that NPM may also determine intracellular localization of FOX

258 its levels in normal cells, suggesting that NPM might modulate FOXM1 level.

259 The NPM-ALK fusion protein is a constitutively-active tyrosi

260 The NPM/B23-binding results in superactivation of ROCK II, w

261 through its ability to selectively bind the NPM 3' UTR and repress NPM translation.

262 changes in protein expression caused by the NPM/ALK fusion, we identified diverse NPM/ALK-induced ch

263 port that T-cell lymphoma cells carrying the NPM-ALK fusion protein (ALK(+) TCL) frequently express t

264 species to the uncoordinated nitrogen of the NPM ligand.

265 that the 3' untranslated region (UTR) of the NPM messenger (m)RNA is sufficient to mediate its transl

266 ufficient for maintaining a low level of the NPM mRNA as well as promoting the commitment of muscle c

267 se a model whereby the downregulation of the NPM mRNA, mediated by HuR, KSRP and its associated ribon

268 Despite the importance of the NPM of the anions, neutral solutes were sorbed much less

269 n (NPM) and the subsequent expression of the NPM-ALK fusion protein.

270 Thus, about 50% of the NPM-ALK is not active and sequestered as NPM-ALK/NPM1 he

271 at the SP cells express higher levels of the NPM-ALK oncogene and are sensitive to an ALK inhibitor.

272 f IL-2Rgamma expression leads to loss of the NPM-ALK protein and, consequently, apoptotic cell death

273 aled that WASp is a central component of the NPM-ALK-dependent actin signaling pathway.

274 LK K210R mutant and by the inhibition of the NPM/ALK function in ALK+ TCL cells by a small-molecule A

275 In few seconds, the NPM ligand modification results in [Ru(III)(NPM-NO)(4-pi

276 Depletion of HuR stabilizes the NPM mRNA, increases NPM protein levels and inhibits myog

277 alignancies that are not associated with the NPM-ALK fusion.

278 -positive (ALK+) ALCL is associated with the NPM-ALK t(2;5) translocation, which is highly correlated

279 Of note, these NPM-ALK+ lymphoma cells overexpress stem cell regulators

280 The unprecedented performance of these NPM catalysts in ORR was attributed to their well-define

281 Thus, NPM-Bax interaction enhances mitochondrial Bax accumulat

282 CD24 competitively inhibits ARF binding to NPM, resulting in decreased ARF, increase MDM2 and decre

283 Conversely, high transient NPM expression enhances c-Myc nucleolar localization, le

284 increased cell death after stress; wild-type NPM or a phosphomimic NPM with a normal phosphorylation

285 n parallel, we generated a similar wild-type NPM trans-genic model (hMRP8-NPM).

286 K into 293T cells showed that only wild-type NPM-ALK increased GLI1 protein levels and activated SHH/

287 own in BaF3 cells transfected with wild-type NPM/ALK and kinase-inactive NPM/ALK K210R mutant and by

288 A proposed [Ru(V)(NPM)(4-pic)2 horizontal lineO](3+) intermediate was not

289 g from doxorubicin treatment in CPC, whereas NPM knockdown alone induces cell death.

290 We, therefore, investigated whether NPM-mutated AMLs have LICs restricted to the CD34(+) fra

291 Mechanisms by which NPM-ALK signaling regulates cell migration, invasion and

292 o-localized with NPM in the cytoplasm, while NPM knockdown led to the disappearance of FOXM1 from the

293 F3 cells into IL-3-independent growth, while NPM-ALK L182R, L256R, L256V, L256P, and L256Q displayed

294 The reason why NPM-ALK succeeds in transforming specifically CD4(+) T l

295 targeted peptides designed to interfere with NPM at distinct functional sites significantly protected

296 Peptides designed to interfere with NPM function were used to explore NPM as a therapeutic t

297 ar FOXM1 was predominantly co-localized with NPM in the cytoplasm, while NPM knockdown led to the dis

298 tion of normal human CD4+ T lymphocytes with NPM-ALK results in their immortalization and malignant t

299 on of normal human CD4(+) T lymphocytes with NPM-ALK results in their malignant transformation.

300 lood and/or bone marrow of 180 patients with NPM-ALK-positive ALCL treated with Berlin-Frankfurt-Muns