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 ule growth rate dependent on the presence of stathmin.

3 ed rapid dephosphorylation and activation of stathmin.

4 le played by MT-interacting proteins such as stathmin.

5 similar to one of the mechanisms utilized by stathmin.

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

7 p1 and the microtubule-destabilizing protein stathmin.

8 can also covalently modify proteins such as stathmin.

9 1) and the microtubule-destabilizing protein stathmin.

10 breast cancer by regulating the function of stathmin.

11 in human breast cancer cells overexpressing stathmin.

12 was impaired by the concomitant deletion of stathmin.

13 t induces proteasome-mediated degradation of stathmin.

14 on as mechanisms for MT growth inhibition by stathmin.

15 r both mechanisms of MT growth inhibition by stathmin.

16 itchlike regulation of the MT mean length by stathmin.

17 dynamics by the signaling proteins Rac1 and stathmin.

18 ich establishes a spatial gradient of active 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 markers, vimentin, snail-2, beta-catenin and stathmin-1 (STMN1) in patient tumors.

24 s-disease transcriptomic analysis identified Stathmin-1 (STMN1), a tubulin-depolymerizing protein, as

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

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

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

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

29 Therefore, we evaluated truncated stathmin-2 (STMN2) as a proxy of TDP-43 pathology, given

30 ionship of TDP-43 pathology with the loss of stathmin-2 (STMN2), an essential protein for axonal grow

31 Reduced stathmin-2 expression is found in neurons trans-differen

32 ion of iPSC-derived motor neurons, rescue of stathmin-2 expression restores axonal regenerative capac

33 mature polyadenylation-mediated reduction in stathmin-2 is a hallmark of ALS-FTD that functionally li

34 binding to sites within the first intron of stathmin-2 pre-messenger RNA, uncover a cryptic polyaden

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

36 ion of the neuronal growth-associated factor stathmin-2.

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

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

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

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

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

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

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

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

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

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

47 Stathmin, a microtubule-destabilizing protein that media

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

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

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

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

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

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

54 of increased vascular leak via modulation of stathmin activity.

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

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

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

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

59 Stathmin, an 18-kDa phosphoprotein that promotes microtu

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

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

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

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

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

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

66 Stathmin and fut8 were identified as downstream targets

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

68 4-HNE were associated with the activation of stathmin and microtubule catastrophe.

69 ics as measured by phosphorylation status of stathmin and microtubule-associated protein 4 (MAP4), th

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

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

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

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

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

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

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

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

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

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

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

81 data identify the essential mammary protein stathmin as protumorigenic and suggest it may serve as a

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

99 In mouse mammary epithelial cells, loss of stathmin compromised the trafficking of polarized protei

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

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

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

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

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

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

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

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

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

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

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

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

112 The stathmin-dependent regulation of nucleation is only acti

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

114 Stathmin depletion reduced the activity of CDC25 and its

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

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

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

118 Moreover, stathmin depresses TTL tubulin tyrosination activity in

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

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

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

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

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

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

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

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

127 We conclude that stathmin expression in demyelinating disorders could hav

128 Reduced stathmin expression in neuroblastoma cells significantly

129 Stathmin expression is critical to maintain oriented cel

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

131 Moreover, inhibiting stathmin expression significantly reduced transendotheli

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

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

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

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

136 We identify STMN2, which encodes a stathmin family protein and is down-regulated in PD brai

137 Stathmin family proteins play major roles during the var

138 pecific cellular locations of members of the stathmin family.

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

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

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

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

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

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

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

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

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

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

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

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

151 generating a stable cell line overexpressing stathmin-GFP.

152 Stathmin has been studied intensively because of its ass

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

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

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

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

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

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

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

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

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

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

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

164 Loss of stathmin in MMTV-Delta16HER2 transgenic mice decreased t

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

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

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

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

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

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

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

172 Stathmin increased the minus end catastrophe frequency a

173 Absence of stathmin induced alterations in mitotic spindle orientat

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

175 Stathmin is a developmentally regulated cytosolic protei

176 Stathmin is a highly conserved MT-regulatory protein tha

177 Stathmin is a microtubule-destabilizing protein ubiquito

178 Stathmin is a ubiquitous microtubule destabilizing prote

179 Stathmin is an important regulator of microtubule polyme

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

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

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

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

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

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

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

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

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

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

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

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

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

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

194 In this study, we report that female stathmin knock-out (STM KO) mice are unable to nurse the

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

225 Arrest of the larval stage in stathmin mutants also reveals a degree of progressive in

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

227 Stathmin mutations disrupt changes in microtubule stabil

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

245 Furthermore, stathmin phosphorylation positively correlated with RSK2

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

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

248 phosphorylation at serine 38 and diminished stathmin protein degradation.

249 We show that Stathmin protein is widely distributed within motoneuron

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

251 disassembly is induced following the loss of Stathmin protein.

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

253 Stathmin proteins can thus be either regulated locally o

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

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

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

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

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

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

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

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

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

263 Stathmin's sequestration activity is well established, b

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

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

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

267 Stathmin steady-state catastrophe-promoting activity was

268 Stathmin (STMN), a cytoplasmic microtubule-destabilizing

269 ough proteomics analysis, we determined that stathmin (STMN1) is affected by EBV-miR-BART6-3p and LOC

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

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

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

273 Finally, stathmin suppression in neuroblastoma cells significantl

274 In conclusion, stathmin suppression interferes with the metastatic proc

275 Stathmin suppression preserved the MT network against th

276 Stathmin suppression significantly reduced neuroblastoma

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

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

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

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

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

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

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

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

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

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

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

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

289 Stathmin was also pathway-pharmacodynamic in vitro and i

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

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

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

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

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

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

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

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.