ライフサイエンスコーパス: separase

1 maintained by securin-mediated inhibition of separase.

2 eady in the active form before activation of separase.

3 tromeric cohesins are removed at anaphase by Separase.

4 important function for the helical region of separase.

5 ors a mutation in At4g22970, the A. thaliana separase.

6 he onset of anaphase due to Scc1 cleavage by separase.

7 Ile-Nle-Arg-MCA) is used as the substrate of separase.

8 to be achieved by inhibition of the protease separase.

9 requires the anaphase-promoting complex and separase.

10 chanism is the inhibitory phosphorylation of separase.

11 is triggered by the cleavage of cohesins by separase.

12 of anaphase through cleavage by the protease separase.

13 gered by the activation of a protease called separase.

14 stroyed at anaphase through Scc1 cleavage by separase.

15 s is mediated by a conserved protease called separase.

16 folding, Cdk1-cyclin B1 acts on native state separase.

17 lin B together with a Cdk1-resistant form of separase.

18 esin is cleaved in metaphase by the protease separase.

19 ycle progression differs from that of fungal separases.

20 grades cyclin B and securin, which activates separase [1].

21 mammalian securin, which is an inhibitor of separase (a protease required for the separation of sist

22 until anaphase, when proteolytic cleavage by separase, a caspase-like enzyme, allows chromosomal sepa

23 It is dissolved in anaphase when separase, a giant cysteine endopeptidase, cleaves the Sc

24 Separase, a protease encoded by the ESPL1 gene, cleaves

25 the destruction of securin, thereby allowing separase, a protease, to disrupt sister-chromatid cohesi

26 cohesion is resolved at anaphase onset when separase, a site-specific protease, cleaves the Scc1 sub

27 Our results indicate that Plk1 and separase act at different times during M phase to licens

28 The sister chromatid-separating protease separase, activated at anaphase onset, interacts with an

29 strate show that the first threshold permits separase activation and chromosome segregation, and the

30 Cytokinesis follows separase activation and chromosome segregation.

31 BUB-1/BUB-3 inhibition equivalently delayed separase activation and other events occurring during mi

32 ng yeast that securin destruction and, thus, separase activation are not sufficient for the efficient

33 hase, i.e., prior to securin destruction and separase activation at anaphase onset.

34 We propose that separase activation at the metaphase-anaphase transition

35 Separase activation results from the destruction of its

36 otation through cyclin B-CDK-1 inactivation, separase activation, or degradation of an unknown dynein

37 sult in delayed mitosis and nonphysiological separase activation.

38 tions and indicate that contacts outside the separase active site are crucial for stabilizing the com

39 When the separase active site was occupied with a peptide inhibit

40 sidues 258-269 of securin are located in the separase active site, illuminating the mechanism of inhi

41 We used this assay to quantify separase activity during cell cycle progression and in a

42 recent evidence in yeast and C. elegans that separase activity is essential for the segregation of re

43 able cyclin B1 or securin, we find here that separase activity is primarily regulated by securin and

44 Cdc6 display lower Cdk1 activity and higher separase activity than cells expressing Cdc6-TV.

45 e challenges of providing protection against separase activity throughout a larger chromosome area.

46 ally swollen4 (rsw4) allele with compromised separase activity, in addition to mitotic failure, displ

47 which occur in other eukaryotes upon loss of separase activity.

48 matid separation (PSCS), suggesting aberrant separase activity.

49 avage by protecting specific substrates from separase activity.

50 chromosome separation through inhibition of separase activity.

51 Thus, separase acts directly on Scc1 and also indirectly, thro

52 isolated the Arabidopsis thaliana homolog of separase (AESP) and investigated its role in somatic and

53 Rather, separase affects nuclear positioning as part of the Cdc1

54 ed a nonphosphorylable point mutant (S1121A) separase allele in securin-/- mouse embryonic stem cells

55 Cleavage of centromeric cohesin by separase allows sister chromatids connected to microtubu

56 e mammary tumors caused by overexpression of Separase, alone or combined with p53 heterozygosity, in

57 Human separase also appears to undergo an autocatalytic proces

58 The alpha-helical region of separase (also known as Esp1) contains four domains (I-I

59 sister chromatids in anaphase is mediated by separase, an endopeptidase that cleaves the chromosomal

60 Separase, an endopeptidase, plays a pivotal role in the

61 precocious centriole disengagement depend on separase and anaphase-promoting complex/cyclosome (APC/C

62 Separase and cohesin are conserved from yeasts to humans

63 cleavage by bridging the interaction between separase and cohesin.

64 dissolution of sister chromatid cohesion by separase and cyclin B destruction is irreversible, it is

65 ported, the atomic structures of full-length separase and especially the complex with securin are unk

66 f sister chromatid cohesion does not require separase and is correlated with a failure of the cohesin

67 structures of the C-terminal two domains of separase and low-resolution electron microscopy reconstr

68 y alterations in the levels of two proteins, separase and Mad2, which are important for maintaining c

69 or securin, which forms a tight complex with separase and may also stabilize this enzyme.

70 exited mitosis after downregulation of both separase and Plk1, centriole disengagement failed comple

71 s and depends on the FEAR network components Separase and Slk19.

72 s atomic mechanisms of substrate cleavage by separase and suggests competitive inhibition by securin.

73 in and cyclin B1, allowing the activation of separase and the onset of anaphase and mitotic exit.

74 ociated cohesins are specifically cleaved by separase and the soluble cohesins are left intact in ana

75 sociated with Cdc20 (APC/C(Cdc20)) activates separase and thereby destroys cohesion along chromosome

76 e system that ensures complete activation of separase and total downregulation of Cdk1 when all chrom

77 , there are no high-resolution structures of separases and the details of their regulation and substr

78 the attenuation of Cdk1 activity, release of separase, and subsequent anaphase progression.

79 (GPI):protein transamidase, metacaspase and separase, and their differences from the clan CA enzymes

80 During metII arrest separase appears primarily regulated by securin binding,

81 role in cleaving the alpha-kleisin subunit, separase appears to have acquired additional diverse act

82 Separases are large proteins that mediate sister chromat

83 Separases are large, 140-250-kilodalton enzymes, with an

84 We identified separase as a key cell cycle component that is required

85 n cleavage is spatiotemporally controlled by separase-associated regulatory proteins, including the i

86 We have previously shown that separase associates with microtubules and regulates micr

87 ent on cohesins that have escaped removal by separase at anaphase onset.

88 are removed when cohesin Scc1 is cleaved by separase at anaphase onset.

89 entriole disengagement requires the protease separase at anaphase, and that this disengagement licenc

90 imetic mutations is no longer protected from separase at centromeres and is cleaved even when the two

91 , and (2) cleavage of centromeric cohesin by separase at the metaphase-anaphase transition.

92 e, isomerization of previously securin-bound separase at the metaphase-to-anaphase transition renders

93 gly, RAD21 is cleaved by a caspase-like Esp1/separase at the onset of anaphase to trigger sister chro

94 cts the expression of ARABIDOPSIS HOMOLOG OF SEPARASE (AtAESP), previously demonstrated to be involve

95 Separase binds to DNA in vitro, but its proteolytic acti

96 that the N-terminal non-catalytic domain of separase binds to the C-terminal tail domain of three ho

97 We developed a separase biosensor in Saccharomyces cerevisiae that prov

98 Loss of separase blocked centriole disengagement during mitotic

99 block the interaction of CDK1/cyclin B1 with separase, both failed to induce sister disjunction.

100 and SAC inactivation, APC/C(Cdc20) activates separase but the resulting loss of (some) cohesion is ac

101 not appear to require the full activation of separase but, instead, triggers a mitotic arrest that de

102 yosin II, the anaphase promoting complex and separase, but did not require cortical contact by the sp

103 mitosis while ensuring timely activation of separase by anaphase-promoting complex/cyclosome-depende

104 show that securin-independent inhibition of separase by Cdk1-cyclin B1 in early mitosis requires the

105 ter chromatid separation is triggered by the separase-catalyzed cleavage of cohesin.

106 vage of the alpha kleisin subunit (Rad21) by separase causes cohesin's dissociation from chromosomes

107 How separase causes PP2A(Cdc55) down-regulation is not known

108 Moreover, depletion of separase causes the accumulation of RAB-11-positive vesi

109 e we report the cloning of full-length human separase cDNA and the characterization of the encoded pr

110 in a conserved motif that partly matches the separase cleavage consensus converts securin from a sepa

111 ore, pericentrin deficiency or mutation of a separase cleavage site blocked DNA damage-induced PCM ex

112 with a reduction in pericentrin-deficient or separase cleavage site mutant-expressing cells, and an i

113 ecific cohesin modification and targeting of separase cleavage.

114 In addition, separase cleaves a similar motif in the kinetochore and

115 Once activated, separase cleaves a subunit of cohesin, a complex that li

116 At the onset of anaphase, separase cleaves cohesin and thereby initiates sister ch

117 DNA is released in anaphase when separase cleaves cohesin's Scc1 subunit.

118 At the cellular level, separase colocalizes with microtubules and RabA2a (for R

119 g to separase facilitate recruitment of Kin7/separase complex (KISC) onto microtubules.

120 Separase, concomitantly with cleaving cohesin, activates

121 iation of Cdk1-cyclin B1 with phosphorylated separase counteracts this tendency and stabilizes separa

122 elivery rates of KNOLLE and RabA2a GTPase in separase-deficient roots.

123 anism governing microtubule dynamics via the separase-dependent activation of CENP-E-related kinesins

124 int if this was not prevented by concomitant separase-dependent activation of the Cdc14 phosphatase.

125 It has been proposed that separase-dependent centriole disengagement at anaphase l

126 enting centriole disengagement by inhibiting separase-dependent cohesin removal.

127 At anaphase onset, separase-dependent down-regulation of PP2A(Cdc55) allows

128 In contrast, separase depletion causes missegregation of both mini- a

129 After fertilization, separase disappeared from these structures and appeared

130 The dynamic pattern of localization of human separase during cell cycle progression differs from that

131 ng sister chromosome separation, the role of separase during cytokinesis is unclear.

132 very that centromeric Rec8 is protected from separase during meiosis I by shugoshin/MEI-S332 proteins

133 PP2A cannot protect centromeric cohesin from separase during meiosis I or support the spindle assembl

134 late cohesin and thereby prevent cleavage by separase during meiosis I.

135 To quantify separase enzymatic activity, we have designed a fluoroge

136 y, there is no quantitative assay to measure separase enzymatic activity.

137 zation of Arabidopsis (Arabidopsis thaliana) separase (ESP) demonstrated that meiotic expression of E

138 rk is comprised of the polo kinase Cdc5, the separase Esp1, the kinetochore-associated protein Slk19,

139 r its meiosis-specific homolog, Rec8, by the separase Esp1.

140 work, including a nonproteolytic function of separase (Esp1); and the mitotic exit network (MEN) driv

141 budding yeast securin/Pds1 not only inhibits separase/Esp1, but also promotes its nuclear localizatio

142 ds1p, an inhibitor of the anaphase activator separase/Esp1p, is involved in several checkpoint pathwa

143 aration and the spindle checkpoint, Mad2 and separase (ESPL1) were increased in null compared with WT

144 mouse mammary transplant model, induction of Separase expression in the transplanted FSK3 cells for 3

145 tionarily conserved caspase-related protease separase (extra spindle poles [ESP]) is required for the

146 The caspase-related protease separase (EXTRA SPINDLE POLES, ESP) plays a major role i

147 onal changes of Kin7 induced upon binding to separase facilitate recruitment of Kin7/separase complex

148 Separase facilitates polar targeting of the auxin efflux

149 the single C-terminal caspase-like domain in separase from C. elegans suggests similar binding modes

150 took an in-depth bioinformatical analysis of separases from different species with respect to their s

151 Loss of separase function during the early mitotic divisions cau

152 In budding yeast, cells lacking separase function exit mitosis with an undivided nucleus

153 Loss of separase function in rsw4 at the restrictive temperature

154 ts essential functions, atomic structures of separase have not been determined.

155 Studies on separase have revealed new levels of regulation of chrom

156 However, among eukaryotes, separases have acquired novel functions.

157 mutation in separase specifically abolished separase hyperphosphorylation in Smad3-deficient cells.

158 APC leads in turn to hyperphosphorylation of separase, impeding chromatid separation.

159 nases capable of phosphorylating Ser-1501 of separase in an in vitro kinase assay.

160 ase counteracts this tendency and stabilizes separase in an inhibited yet activatable state.

161 similar to securin, Cdk1-cyclin B1 regulates separase in both a positive and negative manner.

162 The involvement of separase in both centriole disengagement and sister chro

163 es may be sufficient to protect cohesin from separase in mammalian oocytes.

164 tes independently of proteolytic activity of separase in promoting microtubule rescue and pauses, as

165 is known about the function of the protease separase in promoting sister chromosome separation, the

166 Conditional expression of Separase in tetracycline-inducible diploid FSK3 mouse ma

167 n of rsw4 leads us to hypothesize that plant separase, in addition to cleaving cohesin, regulates cyc

168 of cohesin, which is normally removed by the Separase-independent pathway.

169 : loading by Scc2/4 complex and release by a separase-independent releasing activity as well as by cl

170 Later, recombination stimulates separase-independent removal of REC-8 and COH-3/4 cohesi

171 movements can be restored experimentally by separase-independent resolution of sister chromatid cohe

172 logical and cytogenetic analysis reveal that Separase-induced tumors are clonal in their genomic comp

173 Overexpression of separase induces aneuploidy and mammary tumorigenesis in

174 Overexpression of Separase induces premature separation of chromatids, lag

175 ficance develops aneuploidy within 5 days of Separase induction in vitro.

176 s coupled to Cdk1-cyclin B activity, whereas separase inhibition is maintained by cyclin B concentrat

177 In early anaphase, the previously described separase inhibition of PP2A(Cdc55) promotes cohesin clea

178 e cleavage consensus converts securin from a separase inhibitor to a substrate.

179 e destruction of the mitotic cyclins and the separase inhibitor, securin.

180 spindle assembly checkpoint is securin, the separase inhibitor.

181 nformation and traverse the entire length of separase, interacting with all of its domains.

182 esidues 258-373 of securin (Pds1), named the separase interaction segment, are primarily in an extend

183 Separase is a capase family protease that is required fo

184 Separase is a caspase-family protease required for the m

185 Separase is a cysteine protease with a crucial role in t

186 Our results demonstrate that separase is a key regulator of vesicle trafficking, whic

187 h bearing epithelial tumors, indicating that separase is a tumor suppressor gene in vertebrates.

188 Separase is abruptly activated and cleaves most cohesin

189 Separase is absolutely essential for cohesion dissolutio

190 Once this is achieved, the protease separase is activated to cleave the chromosomal cohesin

191 Separase is also overexpressed and mislocalized in a wid

192 Separase is an endopeptidase that separates sister chrom

193 These results collectively suggest that Separase is an oncogene, whose overexpression alone in m

194 Recent study suggests that separase is an oncogene.

195 Separase is associated with its inhibitor, securin, unti

196 Although separase is essential, securin knock-out mice are surpri

197 fe while Cdk1-cyclin B1-dependent control of separase is essential.

198 Separase is held inactive by association with securin un

199 Vertebrate separase is held inactive by mutually exclusive binding

200 Separase is inhibited by securin, which is degraded at t

201 We show that separase is kept inactive under these conditions by a me

202 Because separase is known to activate Cdc14 (refs 5 and 6), our

203 Separase is known to be inhibited by binding either secu

204 In human tumours separase is overexpressed, making it a potential target

205 Separase is present in the cell during the entire cell c

206 Collectively, these data indicate that separase is required for cytokinesis by regulating the i

207 onucleotides, we report direct evidence that separase is required for high-fidelity chromosome separa

208 ate that a mutation in the mitotic regulator separase is responsible for the cell cycle defects seen

209 The protease activity of separase is strictly regulated by the inhibitor securin,

210 Separase is the protease that cleaves the cohesive link

211 Although most separase is usually found in association with securin, t

212 The caspase family protease, separase, is required at anaphase onset to cleave the co

213 However, separase lacks microtubule-binding activity, raising que

214 Separase localized to cortically located filamentous str

215 We show that separase localizes to the ingressing furrow and midbody

216 In human cells, a fraction of separase localizes to the mitotic chromosome.

217 intact bivalents raised the possibility that separase may also have multiple roles in Arabidopsis.

218 Separase may cleave further substrate proteins to orches

219 entromeric cohesin is protected by Sgo2 from Separase-mediated cleavage ensuring that sister chromati

220 e ability of the spindle checkpoint to delay separase-mediated cleavage of cohesin until entry into a

221 entromeric cohesin is protected by Sgo2 from Separase-mediated cleavage, in order to maintain sister

222 divisions, Rec8 phosphorylation mediates its separase-mediated cleavage.

223 c complementation experiments in conditional separase mutant rsw4 background demonstrate the importan

224 tase suggests that phosphorylation either of separase or cohesin may be necessary for Rec8 cleavage.

225 In budding yeast, the separase ortholog, Esp1, has been shown to cleave a subu

226 osomal cohesin is significantly preferred by separase over Scc1 in soluble cohesin.

227 These results suggest that Separase-overexpressing mammary cells are not only susce

228 In both cases, Separase overexpression bypasses the defect and restores

229 investigate the physiological consequence of Separase overexpression in animals, we have generated a

230 In addition to aneuploidy, Separase overexpression results in chromosomal instabili

231 However, the separase pathway that regulates cohesin dissociation is

232 ependent phosphorylation of Ser-1126 renders separase prone to inactivation by aggregation/precipitat

233 Here we report crystal structures of the separase protease domain from the thermophilic fungus Ch

234 Separase protein and transcripts are overexpressed in a

235 ic MMTV-Espl1 mouse model that overexpresses Separase protein in the mammary glands.

236 Separase protein is found to be significantly overexpres

237 Worms lacking REC-8, or expressing a mutant separase protein with elevated local concentration at ce

238 pendent phosphorylation of Ser-1126 of human separase protein, and (iii) identify kinases capable of

239 AESP is similar to separase proteins identified in other organisms but cont

240 bles differences in substrate specificity of separase proteins to be rationalised.

241 Budding yeast separase recognizes and cleaves two conserved peptide mo

242 This suggests that separase recognizes both a cleavage site consensus seque

243 These structures reveal how separase recognizes cohesin and how cohesin phosphorylat

244 sults suggest that these proteins may act as separase-regulated PP2A(Cdc55) inhibitors.

245 Mutation of a single phosphorylation site on separase relieves the inhibition and rescues chromatid s

246 We report that cohesin cleavage by human separase requires DNA in a sequence-nonspecific manner.

247 Moreover, a separase-resistant allele of the gene coding for the alp

248 Induction of Separase resulted in trisomies for chromosomes 8, 15, an

249 , isomerization also limits the half-life of separase's proteolytic activity, explaining how cohesin

250 Securin(-/-)separase(+/S1121A) cells are viable but fail to maintain

251 The separase-securin complex assumes a highly elongated stru

252 n electron microscopy reconstructions of the separase-securin complex have been reported, the atomic

253 lution of the yeast Saccharomyces cerevisiae separase-securin complex.

254 A residue Ser1126Ala mutation in separase specifically abolished separase hyperphosphoryl

255 metaphase, and it is unclear whether and how separase specifically targets this fraction for cleavage

256 imples (pim, encoding Drosophila Securin) or separase (Sse) suppress, the sensitized phenotype.

257 inhibitor covering the cleavage site motif, separase still efficiently interacted with its substrate

258 s other than the cleavage site motif mediate separase-substrate interaction.

259 We could so far not confirm new separase substrates, but we have uncovered other forms o

260 This is triggered by the protease separase that cleaves the Scc1 subunit of 'cohesin', the

261 romatid cohesion apparatus, and the protease separase that resolves the cohesin complex at the onset

262 age-induced dissociation of cohesin requires separase, the protease that dissolves cohesion in anapha

263 release from chromosomes, or by depletion of separase, the protease that normally drives chromatid se

264 Cdc14 is activated by separase, the protease that triggers sister chromatid se

265 Although securin associates with nascent separase to co-translationally assist proper folding, Cd

266 Zds1 and Zds2 are required downstream of separase to facilitate nucleolar Cdc14 release.

267 DNA repair involves cohesin dissociation by separase to promote accessibility to repair factors duri

268 This liberates separase triggering sister chromatid disjunction and ina

269 At anaphase onset, the protease separase triggers chromosome segregation by cleaving the

270 until cleavage of its Scc1/Rad21 subunit by separase triggers chromosome segregation in anaphase.

271 The protease separase triggers sister separation by cleaving the Scc1

272 Human separase was observed at the poles of the mitotic spindl

273 Activation of Cdc14 by separase was sufficient for Sli15 dephosphorylation and

274 igate substrate recognition by budding yeast separase we analyzed the sequence requirements at one of

275 hat Cdk1-cyclin B1 can also bind and inhibit separase, we investigated whether this kinase might be s

276 The processed forms of human separase were isolated and the identity of the cleavage

277 iated at anaphase onset by the activation of separase, which removes cohesins from chromosomes.

278 ion of the securin Pds1p liberates the Esp1p separase, which ultimately targets the mitotic cohesin M

279 Finally, by depletion of endogenous separase with antisense oligonucleotides, we report dire