ライフサイエンスコーパス: separase

1 sis is released from chromosomes by Wapl and separase.

2 esin is cleaved in metaphase by the protease separase.

3 eady in the active form before activation of separase.

4 tromeric cohesins are removed at anaphase by 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 S1 and PANS2 proteins interact directly with SEPARASE.

9 to be achieved by inhibition of the protease separase.

10 or producing recombinant, securin-free human separase.

11 requires the anaphase-promoting complex and separase.

12 chanism is the inhibitory phosphorylation of separase.

13 is triggered by the cleavage of cohesins by separase.

14 of anaphase through cleavage by the protease separase.

15 gered by the activation of a protease called separase.

16 s is mediated by a conserved protease called separase.

17 maintained by securin-mediated inhibition of separase.

18 important function for the helical region of separase.

19 stroyed at anaphase through Scc1 cleavage by separase.

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

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

22 ycle progression differs from that of fungal separases.

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

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

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

26 intaining genomic stability and dependent on separase, a conserved and essential cohesin protease.

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

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

29 ected diploid cells with siRNA against ESPL1/Separase, a protease responsible for triggering anaphase

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

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

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

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

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

35 Cytokinesis follows separase activation and chromosome segregation.

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

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

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

39 Separase activation results from the destruction of its

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

41 sult in delayed mitosis and nonphysiological separase activation.

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

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

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

45 ains a pseudosubstrate motif that blocks the separase active site.

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

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

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

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

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

51 x/cyclosome (APC/C) activation, including no separase activity, high CDK1 activity, and high cyclin B

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

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

54 avage by protecting specific substrates from separase activity.

55 chromosome separation through inhibition of separase activity.

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

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

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

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

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

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

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

63 Human separase also appears to undergo an autocatalytic proces

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

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

66 phase of mitosis and meiosis is triggered by separase, an evolutionarily conserved protease.

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

68 Separase and cohesin are conserved from yeasts to humans

69 cleavage by bridging the interaction between separase and cohesin.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

88 Separases are large proteins that mediate sister chromat

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

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

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

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

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

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

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

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

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

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

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

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

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

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

103 We developed a separase biosensor in Saccharomyces cerevisiae that prov

104 Loss of separase blocked centriole disengagement during mitotic

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

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

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

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

109 Securins are key regulators of separases, but remain elusive in many organisms due to s

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

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

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

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

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

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

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

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

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

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

120 ecific cohesin modification and targeting of separase cleavage.

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

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

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

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

125 gregation begins when the cysteine protease, separase, cleaves the Scc1 subunit of cohesin at the met

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

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

128 Separase, concomitantly with cleaving cohesin, activates

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

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

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

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

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

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

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

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

137 After fertilization, separase disappeared from these structures and appeared

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

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

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

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

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

143 e provide evidence that this sequence blocks separase engagement of the Scc1 LPE motif.

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

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

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

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

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

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

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

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

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

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

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

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

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

157 Separase facilitates polar targeting of the auxin efflux

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

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

160 Loss of separase function during the early mitotic divisions cau

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

162 Loss of separase function in rsw4 at the restrictive temperature

163 hromosome non-disjunction respectively, when separase function is compromised.

164 ied SEPARASE mutants, showing that PANS1 and SEPARASE have antagonistic functions in vivo.

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

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

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

168 Thus, while caspases and separases have evolved different substrate specificities

169 Here, we demonstrate that the separase homologue Esp1p in the ascomycete Candida albic

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

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

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

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

174 Securin is the key inhibitor of separase in animals and fungi, but has not been identifi

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

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

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

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

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

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

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

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

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

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

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

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

187 Overexpression of separase induces aneuploidy and mammary tumorigenesis in

188 Overexpression of Separase induces premature separation of chromatids, lag

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

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

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

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

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

194 spindle assembly checkpoint is securin, the separase inhibitor.

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

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

197 Separase is a capase family protease that is required fo

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

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

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

201 Separase is a member of the CD clan of cysteine protease

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

203 Separase is abruptly activated and cleaves most cohesin

204 Separase is absolutely essential for cohesion dissolutio

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

206 Separase is also overexpressed and mislocalized in a wid

207 Separase is an endopeptidase that separates sister chrom

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

209 Recent study suggests that separase is an oncogene.

210 Separase is associated with its inhibitor, securin, unti

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

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

213 Separase is held inactive by association with securin un

214 Vertebrate separase is held inactive by mutually exclusive binding

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

216 Separase is inhibited prior to metaphase by the tightly

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

218 Separase is known to be inhibited by binding either secu

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

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

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

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

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

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

225 Separase is the protease that cleaves the cohesive link

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

227 ely sister chromatid separation, promoted by separase, is essential for faithful chromosome segregati

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

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

230 Separase localized to cortically located filamentous str

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

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

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

234 Separase may cleave further substrate proteins to orches

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

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

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

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

239 Separase must be tightly regulated to prevent the untime

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

241 screen for pans1 suppressors, we identified SEPARASE mutants, showing that PANS1 and SEPARASE have a

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

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

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

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

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

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

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

249 However, the separase pathway that regulates cohesin dissociation is

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

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

252 Separase protein and transcripts are overexpressed in a

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

254 Separase protein is found to be significantly overexpres

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

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

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

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

259 Budding yeast separase recognizes and cleaves two conserved peptide mo

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

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

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

263 sults suggest that rapid cohesin cleavage by separase requires a substrate docking interaction outsid

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

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

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

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

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

269 The separase-securin complex assumes a highly elongated stru

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

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

272 We report a role for the C. elegans separase SEP-1, primarily known for its essential activi

273 A residue Ser1126Ala mutation in separase specifically abolished separase hyperphosphoryl

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

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

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

277 To investigate separase substrate specificity and regulation, here we d

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

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

280 n reduces Mcd1p/Scc1p, a cohesin subunit and separase target.

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

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

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

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

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

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

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

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

289 This liberates separase triggering sister chromatid disjunction and ina

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

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

292 The protease separase triggers sister separation by cleaving the Scc1

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

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

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

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

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

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

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

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