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Gene Review

ESPL1  -  extra spindle pole bodies homolog 1 (S....

Homo sapiens

Synonyms: Caspase-like protein ESPL1, ESP1, Extra spindle poles-like 1 protein, KIAA0165, SEPA, ...
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Disease relevance of ESPL1


High impact information on ESPL1

  • Cleavage of cohesin's kleisin subunit by the separase protease then triggers the movement of sister chromatids into opposite halves of the cell during anaphase [2].
  • In vertebrate cells, this process is mediated in part by the protease separase, which destroys a small amount of cohesin, but most cohesin is removed from chromosomes without proteolysis [3].
  • Separase is inhibited by securin, which is degraded at the metaphase-anaphase transition [4].
  • Separation of sister chromatids in anaphase is mediated by separase, an endopeptidase that cleaves the chromosomal cohesin SCC1 [4].
  • Mutation of a single phosphorylation site on separase relieves the inhibition and rescues chromatid separation in extracts with high CDC2 activity [4].

Biological context of ESPL1


Anatomical context of ESPL1


Associations of ESPL1 with chemical compounds


Physical interactions of ESPL1

  • We show that separase is kept inactive under these conditions by a mechanism independent of binding to securin [4].
  • Importantly, proper meiotic maturation is rescued by chemical inhibition of Cdk1 or expression of Cdk1-binding separase fragments lacking cohesin-cleaving activity [7].

Regulatory relationships of ESPL1

  • Separase is activated by the degradation of its inhibitor securin and by the removal of inhibitory phosphates [6].

Other interactions of ESPL1


Analytical, diagnostic and therapeutic context of ESPL1

  • Blocking separase-Cdk1 complex formation by microinjection of anti-separase antibodies prevents polar-body extrusion in vertebrate oocytes [7].
  • The processed forms of human separase were isolated and the identity of the cleavage sites was determined by N-terminal sequencing and site-directed mutagenesis [16].
  • First, Western blot analysis demonstrated that the levels of two proteins involved in regulating sister chromatid separation and the spindle checkpoint, Mad2 and separase (ESPL1) were increased in null compared with WT cells [17].
  • Based on labeling data and sequence analysis, we propose a model for the structure of separase, consisting of 26 ARM repeats, an unstructured region of 280 residues and two caspase-like domains, with securin binding to the ARM repeats [18].


  1. Overexpression and mislocalization of the chromosomal segregation protein separase in multiple human cancers. Meyer, R., Fofanov, V., Panigrahi, A., Merchant, F., Zhang, N., Pati, D. Clin. Cancer Res. (2009) [Pubmed]
  2. The structure and function of SMC and kleisin complexes. Nasmyth, K., Haering, C.H. Annu. Rev. Biochem. (2005) [Pubmed]
  3. Wapl controls the dynamic association of cohesin with chromatin. Kueng, S., Hegemann, B., Peters, B.H., Lipp, J.J., Schleiffer, A., Mechtler, K., Peters, J.M. Cell (2006) [Pubmed]
  4. Dual inhibition of sister chromatid separation at metaphase. Stemmann, O., Zou, H., Gerber, S.A., Gygi, S.P., Kirschner, M.W. Cell (2001) [Pubmed]
  5. Caspase proteolysis of the cohesin component RAD21 promotes apoptosis. Chen, F., Kamradt, M., Mulcahy, M., Byun, Y., Xu, H., McKay, M.J., Cryns, V.L. J. Biol. Chem. (2002) [Pubmed]
  6. Regulation of human separase by securin binding and autocleavage. Waizenegger, I., Giménez-Abián, J.F., Wernic, D., Peters, J.M. Curr. Biol. (2002) [Pubmed]
  7. Essential CDK1-inhibitory role for separase during meiosis I in vertebrate oocytes. Gorr, I.H., Reis, A., Boos, D., Wühr, M., Madgwick, S., Jones, K.T., Stemmann, O. Nat. Cell Biol. (2006) [Pubmed]
  8. Protein phosphatase 2A stabilizes human securin, whose phosphorylated forms are degraded via the SCF ubiquitin ligase. Gil-Bernabé, A.M., Romero, F., Limón-Mortés, M.C., Tortolero, M. Mol. Cell. Biol. (2006) [Pubmed]
  9. The emerging role of pituitary tumor transforming gene in tumorigenesis. Tfelt-Hansen, J., Kanuparthi, D., Chattopadhyay, N. Clinical medicine & research. (2006) [Pubmed]
  10. Mechanism limiting centrosome duplication to once per cell cycle. Tsou, M.F., Stearns, T. Nature (2006) [Pubmed]
  11. Regulation of Separase in meiosis: Separase is activated at the metaphase I-II transition in Xenopus oocytes during meiosis. Fan, H.Y., Sun, Q.Y., Zou, H. Cell Cycle (2006) [Pubmed]
  12. Cdc48 is required for the stability of Cut1/separase in mitotic anaphase. Ikai, N., Yanagida, M. J. Struct. Biol. (2006) [Pubmed]
  13. Basic mechanism of eukaryotic chromosome segregation. Yanagida, M. Philos. Trans. R. Soc. Lond., B, Biol. Sci. (2005) [Pubmed]
  14. Cyclin-B1-mediated inhibition of excess separase is required for timely chromosome disjunction. Holland, A.J., Taylor, S.S. J. Cell. Sci. (2006) [Pubmed]
  15. Protein phosphatase 2A and separase form a complex regulated by separase autocleavage. Holland, A.J., Böttger, F., Stemmann, O., Taylor, S.S. J. Biol. Chem. (2007) [Pubmed]
  16. Processing, localization, and requirement of human separase for normal anaphase progression. Chestukhin, A., Pfeffer, C., Milligan, S., DeCaprio, J.A., Pellman, D. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  17. Hormone-induced chromosomal instability in p53-null mammary epithelium. Pati, D., Haddad, B.R., Haegele, A., Thompson, H., Kittrell, F.S., Shepard, A., Montagna, C., Zhang, N., Ge, G., Otta, S.K., McCarthy, M., Ullrich, R.L., Medina, D. Cancer Res. (2004) [Pubmed]
  18. Domain structure of separase and its binding to securin as determined by EM. Viadiu, H., Stemmann, O., Kirschner, M.W., Walz, T. Nat. Struct. Mol. Biol. (2005) [Pubmed]
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