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Gene Review

Espl1  -  extra spindle pole bodies 1 (S. cerevisiae)

Mus musculus

Synonyms: AL024103, AU045071, Caspase-like protein ESPL1, Cerp, ESP1, ...
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Disease relevance of Espl1

  • Collectively, these experimental data suggest that SSE could be not harmful for women with a history of or at high risk for breast cancer, at least for short treatment periods; however, further studies are needed to thoroughly characterize the activity profile of the extract in this specific setting of patients [1].
  • In this investigation, kallikrein-like prorenin converting enzyme (PRCE C) (mK9) is isolated from genetically inbred high blood pressure (BPH) and their normal counterparts (BPN) mice, and its protein levels are quantitated [2].
  • Mice and rabbits were immunised with sodium salicylate extracts (SSE) prepared from each of 12 serotypes of Pasteurella haemolytica, and the antisera to each were used in cross-indirect haemagglutination (IHA) tests and cross-enzyme-linked immunosorbent assays (ELISA) to study antigenic relationships between the serotypes [3].

High impact information on Espl1

  • Although our work shows that separase is required for sister chromatid separation in higher eukaryotes, in addition, it also indicates that the regulatory proteins have diverged to a surprising degree, particularly in Drosophila [4].
  • However, our genetic analyses show that SSE is essential and required for sister chromatid separation during mitosis [4].
  • Securin binds and inhibits separase, a conserved cysteine endoprotease [4].
  • We have created conditional knockout alleles of the mouse Separase and Securin genes [5].
  • In embryonic fibroblasts, Separase depletion blocks sister chromatid separation but does not prevent other aspects of mitosis, cytokinesis, or chromosome replication [5].

Chemical compound and disease context of Espl1


Biological context of Espl1

  • We therefore investigated if Separase activity is required for correct chromosome segregation in meiosis I in mouse oocytes [6].
  • In yeast and worms, the segregation of homologous chromosomes in meiosis I depends on the APC/C and Separase activity [6].
  • After securin degradation, Separase cleaves the cohesins and triggers chromatid separation, a prerequisite for anaphase [6].
  • One candidate mechanism is the inhibitory phosphorylation of separase [7].
  • Separase: a universal trigger for sister chromatid disjunction but not chromosome cycle progression [5].

Anatomical context of Espl1

  • Yet, it is unclear if Separase is required for the first meiotic division in vertebrates because APC/C activity is thought to be dispensable in frog oocytes [6].
  • We generated a nonphosphorylable point mutant (S1121A) separase allele in securin-/- mouse embryonic stem cells [7].
  • Thus, fibroblasts lacking Separase become highly polyploid [5].
  • Separase depletion in bone marrow causes aplasia and the presumed death of hematopoietic cells other than erythrocytes [5].
  • Hepatocytes stimulated to proliferate in vivo by hepatectomy also become unusually large and polyploid in the absence of Separase but are able to regenerate functional livers [5].

Associations of Espl1 with chemical compounds

  • Separase is a cysteine protease that participates in separation of sister chromatids during mitosis [8].
  • Results obtained provided evidence that MCF-7 tumors did not grow over the treatment period (5 weeks) in ovariectomized females receiving 50 or 100 mg/kg/day SSE (oral route); administration of SSE also did not affect the estradiol-sustained growth of MCF-7 tumors in mice [1].
  • The expression of other genes involved in tumor progression and angiogenesis, such as Thrombospondin 1, Transforming Growth Factor beta2 and Kallikrein 6 was also evaluated in tumor samples, results showing a decrease in mRNA expression upon SSE treatment [1].
  • This antigen was extracted from the SSE with hot phenol/water and analysed by gas chromatography [9].

Enzymatic interactions of Espl1


Other interactions of Espl1

  • Although securin/separase/cohesion pathway was reported to regulate chromosome segregation during meiotic metaphase-to-anaphase transition, little biochemical evidence was provided [11].

Analytical, diagnostic and therapeutic context of Espl1


  1. Lack of stimulatory activity of a phytoestrogen-containing soy extract on the growth of breast cancer tumors in mice. Gallo, D., Ferlini, C., Fabrizi, M., Prislei, S., Scambia, G. Carcinogenesis (2006) [Pubmed]
  2. Kallikrein-like prorenin-converting enzymes in inbred hypertensive mice. Uddin, M., Polley-Mandal, M., Beg, O.U. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  3. Antigenic relationships between the serotypes of Pasteurella haemolytica demonstrable by enzyme-linked immunosorbent assay (ELISA). Burrells, C., Evans, H.B., Dawson, A.M. Vet. Microbiol. (1983) [Pubmed]
  4. Drosophila separase is required for sister chromatid separation and binds to PIM and THR. Jäger, H., Herzig, A., Lehner, C.F., Heidmann, S. Genes Dev. (2001) [Pubmed]
  5. Separase: a universal trigger for sister chromatid disjunction but not chromosome cycle progression. Wirth, K.G., Wutz, G., Kudo, N.R., Desdouets, C., Zetterberg, A., Taghybeeglu, S., Seznec, J., Ducos, G.M., Ricci, R., Firnberg, N., Peters, J.M., Nasmyth, K. J. Cell Biol. (2006) [Pubmed]
  6. The meiosis I-to-meiosis II transition in mouse oocytes requires separase activity. Terret, M.E., Wassmann, K., Waizenegger, I., Maro, B., Peters, J.M., Verlhac, M.H. Curr. Biol. (2003) [Pubmed]
  7. Securin and separase phosphorylation act redundantly to maintain sister chromatid cohesion in mammalian cells. Huang, X., Hatcher, R., York, J.P., Zhang, P. Mol. Biol. Cell (2005) [Pubmed]
  8. Western blot screening for monoclonal antibodies against human separase. Chestukhin, A., DeCaprio, J.A. J. Immunol. Methods (2003) [Pubmed]
  9. Comparison of cell surface antigen extracts from two serotypes of Pasteurella haemolytica. Donachie, W., Gilmour, N.J., Mould, D.L., Poxton, I.R. J. Gen. Microbiol. (1984) [Pubmed]
  10. The selective continued linkage of centromeres from mitosis to interphase in the absence of mammalian separase. Kumada, K., Yao, R., Kawaguchi, T., Karasawa, M., Hoshikawa, Y., Ichikawa, K., Sugitani, Y., Imoto, I., Inazawa, J., Sugawara, M., Yanagida, M., Noda, T. J. Cell Biol. (2006) [Pubmed]
  11. Degradation of securin in mouse and pig oocytes is dependent on ubiquitin-proteasome pathway and is required for proteolysis of the cohesion subunit, Rec8, at the metaphase-to-anaphase transition. Huo, L.J., Zhong, Z.S., Liang, C.G., Wang, Q., Yin, S., Ai, J.S., Yu, L.Z., Chen, D.Y., Schatten, H., Sun, Q.Y. Front. Biosci. (2006) [Pubmed]
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