ライフサイエンスコーパス: stathmin

1 c-jun target genes (cyclin A, beta-PAK, and stathmin).

2 ed rapid dephosphorylation and activation of stathmin.

3 similar to one of the mechanisms utilized by stathmin.

4 but did inhibit interactions with ELK-1 and stathmin.

5 p1 and the microtubule-destabilizing protein stathmin.

6 can also covalently modify proteins such as stathmin.

7 1) and the microtubule-destabilizing protein stathmin.

8 breast cancer by regulating the function of stathmin.

9 in human breast cancer cells overexpressing stathmin.

10 was impaired by the concomitant deletion of stathmin.

11 e regulators and the tubulin-binding protein stathmin.

12 t induces proteasome-mediated degradation of stathmin.

13 on as mechanisms for MT growth inhibition by stathmin.

14 r both mechanisms of MT growth inhibition by stathmin.

15 itchlike regulation of the MT mean length by stathmin.

16 dynamics by the signaling proteins Rac1 and stathmin.

17 ich establishes a spatial gradient of active stathmin.

18 ule growth rate dependent on the presence of stathmin.

19 The oncoprotein stathmin 1 (STMN1) is upregulated in most, if not all, c

20 questration of the MT depolymerizing protein Stathmin 1 (STMN1), and we provide evidence that STAT3 m

21 paranodal microtubule destabilizing protein, stathmin 1, and the paranodal cell adhesion molecules ne

22 osphorylation sites originally identified in stathmin 1, we show here that they possess distinct phos

23 reporter proteins and endogenously expressed stathmin-1 and insulin-like growth factor-1 receptor.

24 teract with the growth cone-enriched protein stathmin 2, are packaged into vesicles and are carried t

25 uces a redistribution of stathmin 3, but not stathmin 2, from the periphery toward the Golgi region o

26 We also show for the first time that, unlike stathmin 2, stathmin 3 is a substrate for glycogen synth

27 We have shown previously that stathmins 2 (SCG10) and 3 (SCLIP) fulfill distinct, inde

28 th are microtubule modifiers, such as SCG10 (Stathmin-2).

29 for the first time that, unlike stathmin 2, stathmin 3 is a substrate for glycogen synthase kinase (

30 Interestingly, stathmin 3 phosphorylated at its GSK-3beta target site d

31 ion of GSK-3beta induces a redistribution of stathmin 3, but not stathmin 2, from the periphery towar

32 ow that increasing the concentration of Op18/stathmin, a component of the chromosome-mediated microtu

33 study, we report the increased expression of stathmin, a developmentally regulated tubulin-binding pr

34 t mice without an inhibitor of microtubules, stathmin, a gene enriched in BLA-associated circuitry, h

35 Therefore, targeting stathmin, a gene product that is overexpressed in the pr

36 egulator of microtubules, we next focused on stathmin, a known ERK substrate.

37 Depletion of stathmin, a microtubule (MT) destabilizer, delays mitoti

38 We found that inhibition of stathmin, a microtubule regulator that can be transcript

39 Stathmin, a microtubule-destabilizing protein that media

40 e stability and decreased phosphorylation of stathmin, a microtubule-destabilizing protein, at serine

41 KIS is a protein kinase that associates with stathmin, a modulator of the tubulin cytoskeleton.

42 Here we demonstrate that Stathmin, a protein that associates with microtubules an

43 ts, and (3) contact the N-terminal region of stathmin, a protein that induces depolymerization of tub

44 h microtubule-associated protein (MAP) 4 and stathmin, a tubulin-interacting protein.

45 Stathmin accumulated in the cytoplasm of 30% of spinal c

46 Inhibition of stathmin activity by small interfering RNA-based knockdo

47 of increased vascular leak via modulation of stathmin activity.

48 Stathmin (also known as oncoprotein 18/Op18) is a promin

49 hreonine kinase KIS (Kinase Interacting with Stathmin, also known as UHMK1) have recently been associ

50 y sequestering tubulin; the other holds that stathmin alters microtubule dynamics by directly destabi

51 rom embryonic rat cerebral cortex identified stathmin among several differentially expressed proteins

52 Stathmin, an 18-kDa phosphoprotein that promotes microtu

53 tions but had no effect on interactions with stathmin, an ERK substrate whose docking site is unknown

54 We have identified stathmin, an inhibitor of microtubule formation, as high

55 ion is exerted by modulating the activity of stathmin, an MT-destabilizing protein, and by direct bin

56 ion of the microtubule-destabilizing protein stathmin and 2) phosphorylation and inactivation of GSK-

57 highlighted three focal proteins: vimentin, stathmin and cofilin-1, belonging to or involved in cyto

58 on; and (e) hydrogen peroxide down-regulated stathmin and disrupted the cellular microtubule network.

59 Stathmin and fut8 were identified as downstream targets

60 we show that activated STAT3 interacted with stathmin and inhibited its microtubule-destabilizing act

61 4-HNE were associated with the activation of stathmin and microtubule catastrophe.

62 monstrates that RSK2 directly phosphorylates stathmin and regulates microtubule polymerization to pro

63 ns in vitro and demonstrate that full-length stathmin and TTL compete for binding to tubulin and fail

64 Stathmin and tubulin tyrosine ligase (TTL) each form sta

65 issues, we have studied interactions between stathmin and varied tubulin polymers.

66 cylc-1 and -2, share sequence homology with stathmins and encode small, very basic proteins containi

67 number of astral microtubules was similar in stathmin +/+ and -/- MEFs.

68 wo alpha:beta tubulin dimers per molecule of stathmin), and by increasing the switching frequency (ca

69 CD79b, octamer binding factor 1, Ig H chain, stathmin, and gamma-actin.

70 , dihydrofolate reductase, thymidine kinase, stathmin, and MAP4 were down-regulated.

71 These findings highlight stathmin as a possible biomarker of MCC and as a target

72 These data implicate stathmin as a regulator of the microtubule network durin

73 The findings implicate stathmin as the critical molecular component linking the

74 tubule (MT) proteomic work revealed that the stathmin association with MTs is considerably reduced in

75 that RSK2 directly binds and phosphorylates stathmin at the leading edge of cancer cells.

76 and Plk1 are likely regulated downstream of stathmin, because the combination of stathmin knockdown

77 We show that stathmin binds tightly to Dolastatin-10 tubulin rings, w

78 m of any direct action is mysterious because stathmin binds to microtubules very weakly.

79 ofluorescence microscopy, we also found that stathmin binds to purified microtubules along their leng

80 The direct inhibition of stathmin by CCNU is likely a contributing factor.

81 the cellular microtubule-associated protein stathmin by its known association with the cellular phos

82 Phosphorylation of stathmin by RSK2 reduced stathmin-mediated microtubule d

83 Silencing of stathmin by small interfering RNA (siRNA) in mutant p53

84 le-destabilizing effect of an excess of Op18/stathmin can be partially overcome by expression of cons

85 of microtubule regulatory proteins that like stathmin can bind to soluble tubulin and depolymerize mi

86 The results firmly establish that stathmin can increase the steady-state catastrophe frequ

87 Taken together, our results suggest that stathmin can promote catastrophe by direct action on pro

88 tributed within motoneurons and that loss of Stathmin causes impaired NMJ growth and stability.

89 genitors were transfected using a myc-tagged stathmin cDNA and were allowed to differentiate.

90 only active in interphase; overexpression of stathmin-CFP did not impact metaphase microtubule nuclea

91 For a homogeneous stathmin concentration in the absence of Rac1, we find a

92 al simulations to determine the steady-state stathmin concentration, the mean MT length distribution,

93 ormatic analyses, we show that p27(kip1) and stathmin conjunctly control activation of the MAPK pathw

94 In MEFs, the relative amount of stathmin corresponded to genotype, where cells heterozyg

95 e kidney epithelial (LLCPK) cells expressing stathmin-cyan fluorescent protein (CFP) or injected with

96 in in vitro assays and cells overexpressing stathmin-cyan fluorescent protein.

97 siRNA-induced repression of stathmin decreased cell proliferation, viability and clo

98 -/-) VSMCs fully restored the phenotype, and stathmin-deficient mice demonstrated reduced lesion form

99 S-/- VSMCs fully restored the phenotype, and stathmin-deficient mice demonstrated reduced lesion form

100 ss induce proteome-wise alterations, such as stathmin degradation and disorganization of the cell mic

101 ustained expression of constitutively active stathmin delayed cytoplasmic maturation (ie, glycoprotei

102 These results demonstrate the mechanism of stathmin-dependent control of MT dynamics, Rho signaling

103 The stathmin-dependent regulation of nucleation is only acti

104 ent of Plk1 to the centrosome was delayed in stathmin-depleted cells, independent of MTs.

105 Stathmin depletion reduced the activity of CDC25 and its

106 zation to the centrosome required MTs, while stathmin depletion spread its localization beyond that o

107 lymerizing MTs with nocodazole abrogates the stathmin-depletion induced cell cycle delay; in this stu

108 imic curved tubulin protofilaments, and that stathmin depolymerizes stabilized protofilament-rich pol

109 Moreover, stathmin depresses TTL tubulin tyrosination activity in

110 Plk1 was inhibited by excess stathmin, detected in in vitro assays and cells overexpr

111 Although overexpression of stathmin did not result in nonadherent growth, inhibitio

112 oncomitant deletion of stathmin in p27(kip1)/stathmin double-KO mice, suggesting that a CDK-independe

113 To explore the importance of stathmin down-regulation during megakaryocytopoiesis, we

114 We explored the functions of stathmin down-regulation in activated macrophages by gen

115 an be regulated through inactivation of Op18/stathmin downstream of Rac1 and Pak in vivo.

116 These data define a required function for Stathmin during synapse maintenance in a model system in

117 Stathmin, encoded by the signature gene STMN1, was an ac

118 ed to genotype, where cells heterozygous for stathmin expressed half as much stathmin mRNA and protei

119 hese findings suggest that the inhibition of stathmin expression and function may be useful in limiti

120 ed p53/21(WAF1/Cip1) regulatory pathways for stathmin expression and function.

121 We conclude that stathmin expression in demyelinating disorders could hav

122 Reduced stathmin expression in neuroblastoma cells significantly

123 We show that decreases in stathmin expression lead to significant decreases in mal

124 Moreover, inhibiting stathmin expression significantly reduced transendotheli

125 impaired in MKs in which down-regulation of stathmin expression was prevented.

126 phosphorylation, each phosphoprotein of the stathmin family fulfilling distinct and specific roles i

127 bound by stathmin or by the SLD of RB3, two stathmin family members that have been extensively studi

128 protein) is a neuron specific member of the stathmin family of microtubule regulatory proteins that

129 Stathmin family proteins play major roles during the var

130 pecific cellular locations of members of the stathmin family.

131 Remarkably, stathmin(-/-) females have an enhancement in social inte

132 ow that the deficiency in fear processing in stathmin(-/-) females leads to improper threat assessmen

133 ficiency is observed in maternal behavior of stathmin(-/-) females: they lack motivation for retrievi

134 e, we selected for modeling the complex of a stathmin fragment with two tubulin heterodimers with two

135 CopN displaces stathmin from preformed stathmin-tubulin complexes, indi

136 We examined stathmin function in two cell systems: mouse embryonic f

137 ne, enabling future genetic investigation of Stathmin function with potential relevance to the cause

138 These data support a model in which stathmin functions in interphase to control the partitio

139 by maternal nutrient restriction: caveolin, stathmin, G-1 cyclin, alpha-actin, titin, cardiac ankyri

140 lated from embryos +/+, +/-, and -/- for the stathmin gene and porcine kidney epithelial (LLCPK) cell

141 model system in which there is only a single stathmin gene, enabling future genetic investigation of

142 We show that stathmin-GFP overexpression impacts MT stability, impair

143 generating a stable cell line overexpressing stathmin-GFP.

144 Stathmin has been studied intensively because of its ass

145 The microtubule-destabilizing protein, stathmin, has recently been shown to mediate neuroblasto

146 These results suggest either that TTL and stathmin have a partially overlapping footprint on the t

147 Stathmin immunohistochemistry in adult rodent brain reve

148 Stathmin immunoreactivity was also associated with neuro

149 In physiological conditions, stathmin immunoreactivity was observed in polysialic aci

150 icate that an important regulatory action of stathmin in cells may be to destabilize microtubule minu

151 n, implicating a pivotal inhibitory role for stathmin in classically activated macrophages.

152 Overexpression of Stathmin in HeLa cells was associated with collapse of m

153 Downregulation of stathmin in KIS(-/-) VSMCs fully restored the phenotype,

154 Downregulation of stathmin in KIS-/- VSMCs fully restored the phenotype, a

155 We therefore sought to establish a role for stathmin in malignant glioma cell motility, migration, a

156 On the other hand, stathmin in mature OLs may indicate cell stress and poss

157 l role of the microtubule-associated protein stathmin in MCPyV ST-mediated microtubule destabilizatio

158 mice is reverted by concomitant deletion of stathmin in p27(kip1)/stathmin double-KO mice, suggestin

159 his controversy and investigated the role of stathmin in primary human MKs.

160 em to prevent physiologic down-regulation of stathmin in primary MKs.

161 the involvement of the MT-associated protein stathmin in the mediation of agonist-induced permeabilit

162 These results suggest a role for stathmin in the migration of newborn neurons in the adul

163 x treatment altered little the expression of stathmin in the parental cell line, although it increase

164 erine 16 or 63 is sufficient to inhibit Op18/stathmin in vitro.

165 by siRNA, suggesting participation of these stathmins in granule formation or maturation.

166 The disassembly of the NMJ in stathmin includes a predictable sequence of cytological

167 Stathmin increased the minus end catastrophe frequency a

168 pping footprint on the tubulin dimer or that stathmin induces a tubulin conformation incompatible wit

169 Stathmin is a developmentally regulated cytosolic protei

170 Stathmin is a highly conserved MT-regulatory protein tha

171 Stathmin is a microtubule-destabilizing protein ubiquito

172 Stathmin is a ubiquitous microtubule destabilizing prote

173 Stathmin is an important regulator of microtubule polyme

174 These studies indicate that suppression of stathmin is biologically important for MK maturation and

175 constitutively active Rac1 at the cell edge, stathmin is deactivated locally, which establishes a spa

176 In the early phase, stathmin is dephosphorylated, enhancing its microtubule-

177 Stathmin is known to form a tight 1:2 complex with tubul

178 ial task dependent on the hippocampus, where stathmin is not normally expressed.

179 e regulated by cytosolic stathmin, while the stathmin is regulated by Rac1 at the membrane.

180 We therefore conclude that stathmin is required for the induction of LTP in afferen

181 Op18 (Oncoprotein 18, Stathmin) is a mitotic regulator that is highly expresse

182 Op18 (Oncoprotein 18, Stathmin) is an important mitotic regulator that is high

183 e results, together with the decrease of one Stathmin isoform, suggest a role of the protein in Golgi

184 Kinase-interacting stathmin (KIS) is a growth factor-dependent nuclear kina

185 Transfection of CECs with kinase-interacting stathmin (KIS) siRNA was performed.

186 Kinase interacting with stathmin (KIS) targets 2 key regulators of cell prolifer

187 Kinase interacting with stathmin (KIS) targets 2 key regulators of cell prolifer

188 at Ser10 was mediated by kinase-interacting stathmin (KIS), confirmed with siRNA to KIS, and phospho

189 ream of stathmin, because the combination of stathmin knockdown and inhibition of Aurora A and Plk1 w

190 The protective effects of stathmin knockdown were observed in vivo in the mouse 2-

191 from amygdala slices that are isolated from stathmin knockout mice show deficits in spike-timing-dep

192 In contrast, stathmin level had a significant effect on microtubule n

193 Increased stathmin level in LLCPK cells, sufficient to reduce micr

194 re and after the down-regulation of cellular stathmin levels and in the absence and presence of suble

195 However, sustained stathmin levels in differentiating OLs, because of overe

196 ucleation rate from centrosomes, where lower stathmin levels increased nucleation and higher stathmin

197 thmin levels increased nucleation and higher stathmin levels reduced nucleation.

198 In MS patients, however, stathmin levels were elevated in 2',3'-cyclic nucleotide

199 , we show that there is a global decrease in stathmin levels, an MT catastrophe protein, in activated

200 Aged wild-type mice show impairments in stathmin levels, changes in microtubule stability and Gl

201 o test the biological relevance of increased stathmin levels, primary OL progenitors were transfected

202 of p21(WAF1/Cip1), but caused no changes in stathmin levels.

203 aspanin 2 (Tspan2), peroxiredoxin 4 (Prdx4), stathmin-like 2 (Stmn2), myelin oligodendrocyte glycopro

204 ions were for bone marrow stromal antigen 2, stathmin-like 3, tumor necrosis factor receptor superfam

205 Here, we design and characterize new stathmin-like domain (SLD) proteins that sequester tubul

206 tered expression of adducin-alpha, pallidin, stathmin-like-2, and synaptojanin-2 binding protein.

207 hus, the signature or its components such as stathmin may be clinically useful tests for stratificati

208 tion back to control levels, indicating that stathmin may influence these processes in neuroblastoma

209 We hypothesized that by reversing stathmin-mediated depolymerization of microtubules or by

210 We previously identified stathmin-mediated mechanisms of resistance to antimicrot

211 Phosphorylation of stathmin by RSK2 reduced stathmin-mediated microtubule depolymerization.

212 st excessive neointima formation by opposing stathmin-mediated VSMC migration and that VSMC migration

213 monstrated by results showing that CTLs from stathmin(-/-) mice displayed defective MTOC polarization

214 to the synapse, allowing it to phosphorylate stathmin molecules near the immunological synapse.

215 n in the Rac- and Cdc42-dependent PAK1/2 and stathmin molecules.

216 rozygous for stathmin expressed half as much stathmin mRNA and protein as wild-type cells.

217 In particular, we consider a Rac1-stathmin-MT pathway in which the growth and catastrophe

218 ion of either wild type or a phospho-mimetic stathmin mutant (4E) made defective in tubulin binding r

219 GluA2 endocytosis rescues memory deficits in stathmin mutant and aged wild-type mice.

220 le expression of a phosphorylation-deficient stathmin mutant exacerbated thrombin-induced EC barrier

221 In addition, we show that stathmin mutants display evidence of defective axonal tr

222 Stathmin mutations disrupt changes in microtubule stabil

223 hese clones (cardiac alpha-actin, cyclin G1, stathmin, NADH dehydrogenase subunit 2, titin and prosta

224 Our results indicate that the effects of stathmin on dynamic instability are strongly but differe

225 ylation of the individual serine residues of stathmin on microtubule dynamic instability have not bee

226 Phosphorylation of stathmin on one or more of its four serine residues (Ser

227 Oncoprotein 18/Stathmin (Op18) is a microtubule-destabilizing protein t

228 ion of the microtubule destabilizing protein stathmin/Op18 in the nascent axon and that this event is

229 nt from two, the number of tubulins bound by stathmin or by the SLD of RB3, two stathmin family membe

230 Reducing the expression of stathmin or doublecortin with an antisense oligonucleoti

231 We found that targeting stathmin or wee-1 expression with RNA interference can i

232 )/M progression, respectively, and sensitize stathmin-overexpressing breast cancer cells to paclitaxe

233 he trans-Golgi protein SCLIP (STMN3) and its stathmin paralog SCG10 (STMN2) for functional study.

234 Furthermore, knockdown of stathmin partially restored cell-cycle regulation and ac

235 Therefore, the RSK2-stathmin pathway represents a promising therapeutic targ

236 yielded a binding stoichiometry of 1 mol of stathmin per approximately 14.7 mol of tubulin in the mi

237 ein levels, caused by a lack of KIS-mediated stathmin phosphorylation at serine 38 and diminished sta

238 Supporting an important role of stathmin phosphorylation in T cell activation, we showed

239 the physiological relevance of KIS-mediated stathmin phosphorylation in VSMCs are unknown.

240 the physiological relevance of KIS-mediated stathmin phosphorylation in VSMCs are unknown.

241 Furthermore, stathmin phosphorylation positively correlated with RSK2

242 These results suggest that stathmin plays an essential role in anchorage-independen

243 These observations lead us to propose that stathmin promotes catastrophe by binding to and acting u

244 One model is that stathmin promotes microtubule catastrophe indirectly, an

245 phosphorylation at serine 38 and diminished stathmin protein degradation.

246 result in nonadherent growth, inhibition of stathmin protein expression by antisense oligonucleotide

247 We show that Stathmin protein is widely distributed within motoneuron

248 omigratory phenotype resulted from increased stathmin protein levels, caused by a lack of KIS-mediate

249 disassembly is induced following the loss of Stathmin protein.

250 n fluorescent protein (CFP) or injected with stathmin protein.

251 Stathmin proteins can thus be either regulated locally o

252 Furthermore, overexpressing stathmin reduces complement receptor 3-mediated phagocyt

253 These data demonstrate that stathmin regulates mitotic entry, partially via MTs, to

254 In several cell types, stathmin regulates the partitioning of tubulin between u

255 ion, in neuroblastoma cells highlighted that stathmin regulates transendothelial migration through RO

256 Reduction or loss of stathmin resulted in increased microtubule polymer but l

257 In this study we investigated stathmin's contribution to the metastatic process and po

258 Moreover, we suggest that stathmin's minus-end preference results from interaction

259 preference results from interactions between stathmin's N terminus and the surface of alpha-tubulin t

260 show that these mechanisms could account for stathmin's observed activities in vitro, but that both t

261 Stathmin's sequestration activity is well established, b

262 er, overexpression of phospho-mimetic mutant stathmin S16D significantly rescued the decreased invasi

263 Although CopN and stathmin share no detectable sequence identity, both inf

264 Here we analyzed the effects of stathmin singly phosphorylated at Ser(16) or Ser(63), an

265 ind that, in vitro, Pak1 phosphorylates Op18/stathmin specifically at serine 16 and inactivates its c

266 Stathmin steady-state catastrophe-promoting activity was

267 Stathmin (STMN), a cytoplasmic microtubule-destabilizing

268 Here we show that stathmin strongly destabilizes microtubule minus ends in

269 with its ability to destabilize minus ends, stathmin strongly increased the treadmilling rate of bov

270 eins dihydropyrimidinase-related protein and stathmin suggested mechanisms for rapid cytoskeletal reo

271 Finally, stathmin suppression in neuroblastoma cells significantl

272 In conclusion, stathmin suppression interferes with the metastatic proc

273 Stathmin suppression preserved the MT network against th

274 Stathmin suppression significantly reduced neuroblastoma

275 ce of the fact that the lateral diffusion of stathmin tends to weaken the effects of Rac1 on the dist

276 For tubulin sequestering by stathmin, this establishes a bistable switch with two st

277 oxiredoxin 1 and down-regulation (by 25%) of stathmin through proteasome-mediated degradation; and (e

278 strongly reduced or abolished the ability of stathmin to bind to and sequester soluble tubulin and it

279 These findings highlight the importance of stathmin to the metastatic process and its potential as

280 5) and Ser(38) did not affect the binding of stathmin to tubulin or microtubules or its catastrophe-p

281 the presence of a 1:5 initial molar ratio of stathmin to tubulin yielded a binding stoichiometry of 1

282 to tubulin and fail to make a stable tubulin:stathmin:TTL triple complex in solution.

283 rotubule-destabilizing activity by promoting stathmin-tubulin binding, whereas in the late phase thes

284 bulin strongly inhibits formation of the 1:2 stathmin-tubulin complex (>3.3 kcal/mol), while ER-07634

285 CopN displaces stathmin from preformed stathmin-tubulin complexes, indicating that the proteins

286 strophe frequency approximately 13-fold at a stathmin:tubulin molar ratio of 1:5.

287 Stathmin was also pathway-pharmacodynamic in vitro and i

288 In addition, using mass spectrometry, stathmin was identified as the main component of a speci

289 cells, the active nonphosphorylated form of stathmin was increased approximately 2-fold, whereas the

290 For catastrophe-promoting stathmin, we do not find bistability.

291 Increased levels of stathmin were confirmed by Western blot analysis of norm

292 Mutations in Drosophila stathmin were isolated in two independent genetic screen

293 argeting wee-1 led to the phosphorylation of stathmin, which is known to attenuate its activity.

294 the MT growth rate is inhibited by cytosolic stathmin, which, in turn, is inactivated by Rac1.

295 ophe rates of MTs are regulated by cytosolic stathmin, while the stathmin is regulated by Rac1 at the

296 onadherent growth, we investigated one gene, stathmin whose upregulation by cJun was observed only un

297 ealed that the tubulin-destabilizing protein Stathmin, whose expression also confers resistance to pa

298 In contrast to stathmin, whose major action on dynamics is to destabili

299 Protein profiling showed dysregulation of Stathmin with a marked decrease of its most acidic and p

300 ntimitotic peptides mimic the interaction of stathmin with tubulin.