Affinage

ESPL1

Separin · UniProt Q14674

Round 2 corrected
Length
2120 aa
Mass
233.2 kDa
Annotated
2026-04-28
78 papers in source corpus 23 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ESPL1 (separase) is a cysteine endopeptidase that triggers sister chromatid separation at the metaphase-to-anaphase transition by cleaving the cohesin subunit SCC1/RAD21 and additionally cleaves the centrosomal protein kendrin/pericentrin to license centriole disengagement and duplication (PMID:11509732, PMID:22542101, PMID:19758559). Separase is held inactive during early mitosis by two cooperative mechanisms: securin binding, which occludes the active site via pseudosubstrate motifs, and CDK1–cyclin B1 complex formation stabilized by a phosphoserine on separase that engages cyclin B1, deploying autoinhibitory loops; APC/C-mediated destruction of both securin and cyclin B1 at anaphase onset releases these dual brakes (PMID:9635435, PMID:11747808, PMID:34290405). Upon activation, separase undergoes autocatalytic processing and its N-terminal domain functions as a direct CDK1 inhibitor independent of its protease activity (PMID:12194817, PMID:15989971). Overexpression of separase causes premature chromatid separation, aneuploidy, and mammary tumorigenesis in transgenic mice, and ESPL1 is overexpressed in human breast tumors (PMID:18728194, PMID:24276237).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1998 High

    The foundational question of how sister chromatids separate at anaphase was answered by showing that APC-mediated securin destruction liberates separase (Esp1), which is required for cohesin dissociation from chromosomes.

    Evidence Genetic epistasis and co-immunoprecipitation in budding yeast

    PMID:9635435

    Open questions at the time
    • Mechanism of cohesin removal unknown (direct cleavage vs. displacement)
    • Vertebrate separase not yet identified
  2. 1999 High

    Extension of the securin–separase axis to vertebrates established its universal role: vertebrate securin (PTTG) binds and inhibits separase, and non-degradable securin blocks chromatid separation without halting cell cycle progression.

    Evidence Biochemical pulldown and cell-free Xenopus egg extract assays with stable securin mutants in mammalian cells

    PMID:10411507

    Open questions at the time
    • Direct substrate of vertebrate separase not identified
    • Mechanism of inhibition not resolved structurally
  3. 2001 High

    Two key mechanistic questions were resolved simultaneously: human separase directly cleaves the cohesin subunit SCC1 at defined sites (required for both anaphase and cytokinesis), and separase is dually inhibited by securin binding and CDK1-dependent phosphorylation, with each mechanism sufficient independently.

    Evidence Site-directed mutagenesis of SCC1 cleavage sites in human cells; Xenopus egg extract reconstitution with phospho-mutant separase and quantitative mass spectrometry

    PMID:11509732 PMID:11747808

    Open questions at the time
    • Structural basis of dual inhibition unknown
    • Whether CDK1 phosphorylation acts by direct active-site blockade or allosteric mechanism unclear
  4. 2002 High

    The question of whether separase is regulated post-activation was addressed by demonstrating autocatalytic processing upon securin degradation; securin inhibits separase by blocking substrate access, and processed fragments remain associated.

    Evidence In vitro inhibitor binding assays, RNAi, and site-directed mutagenesis in human cells

    PMID:12194817

    Open questions at the time
    • Biological significance of autocatalytic cleavage unknown
    • Whether processed separase has altered activity or stability unclear
  5. 2003 High

    Full-length human separase was cloned and shown to localize to spindle poles until anaphase onset, when it abruptly dissociates; autocatalytic cleavage sites were mapped, establishing the spatial regulation of separase activity.

    Evidence cDNA cloning, immunofluorescence, N-terminal sequencing, antisense knockdown in human cells

    PMID:12672959

    Open questions at the time
    • Mechanism of spindle pole targeting unknown
    • Whether spindle pole dissociation is required for cohesin cleavage unclear
  6. 2005 High

    Separase was revealed to have a non-proteolytic function as a direct CDK1 inhibitor: CDK1–cyclin B1 forms a stable complex with phosphorylated separase, and the complex mutually inhibits both protease and kinase activities, with securin negatively regulating this interaction.

    Evidence In vitro kinase and protease assays with co-immunoprecipitation and mutagenesis

    PMID:15989971

    Open questions at the time
    • Physiological significance of CDK1 inhibition by separase during mitotic exit unclear
    • Quantitative contribution relative to cyclin B1 degradation not measured
  7. 2008 High

    Separase was shown to have essential anaphase functions beyond cohesin cleavage: Esp1 protease activity is required for spindle elongation independently of Mcd1 cleavage, implying a second spindle-associated substrate.

    Evidence Temperature-sensitive mutant analysis with ectopic TEV cleavage of Mcd1 in budding yeast

    PMID:18430955

    Open questions at the time
    • Identity of the second spindle substrate unknown
    • Whether this non-cohesin substrate is conserved in vertebrates unclear
  8. 2008 High

    Separase overexpression was directly linked to oncogenesis: overexpression in mammary epithelial cells caused premature chromatid separation, aneuploidy, and mammary tumorigenesis in vivo, with separase overexpressed in human breast tumors.

    Evidence Tetracycline-inducible conditional expression and in vivo mammary transplant model in mice

    PMID:18728194

    Open questions at the time
    • Mechanism by which excess separase activity is oncogenic (aneuploidy vs. other functions) not dissected
    • Driver vs. passenger role in human tumors not resolved
  9. 2009 High

    A new cellular role for separase was established: it is required for centriole disengagement at mitotic exit, functioning in parallel with Plk1; combined loss abolishes centriole duplication licensing.

    Evidence RNAi knockdown with timed Plk1 inhibition in human cells, live-cell imaging

    PMID:19758559

    Open questions at the time
    • Direct centrosomal substrate of separase unknown at this point
    • Whether separase acts at centrosomes via proteolysis or another mechanism unclear
  10. 2012 High

    The centrosomal substrate question was resolved: separase cleaves kendrin/pericentrin at a consensus site in vivo and in vitro, and this cleavage is required for centriole disengagement and subsequent duplication.

    Evidence In vitro cleavage assay, non-cleavable mutant expression, and centriole imaging in human cells

    PMID:22542101

    Open questions at the time
    • Whether additional centrosomal substrates exist unknown
    • Regulation of separase specificity toward centrosomal vs. cohesin substrates not resolved
  11. 2021 High

    The long-standing question of how dual inhibition works at the structural level was answered: cryo-EM structures revealed that securin uses pseudosubstrate motifs to block the active site, while CDK1–cyclin B1 deploys autoinhibitory loops from separase's own disordered regions and a phosphoserine–cyclin B1 interaction stabilizes the inhibitory complex.

    Evidence Cryo-EM structure determination of human separase–securin and separase–CDK1–cyclin B1–CKS1 complexes

    PMID:34290405

    Open questions at the time
    • Structure of active (uninhibited) separase not determined
    • Conformational changes during substrate engagement unknown
    • Mechanism of autocatalytic cleavage not resolved structurally

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structure of active separase, the identity of additional non-cohesin substrates in vertebrates, the physiological significance of the interphase lamin interaction, and whether separase-dependent CDK1 inhibition has a non-redundant role in mitotic exit control.
  • No structure of active uninhibited separase
  • Vertebrate non-cohesin spindle substrate not identified
  • Lamin interaction not confirmed in peer-reviewed study
  • Quantitative contribution of separase-mediated CDK1 inhibition to mitotic exit unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0098772 molecular function regulator activity 1
Localization
GO:0005815 microtubule organizing center 3 GO:0005694 chromosome 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-1640170 Cell Cycle 8 R-HSA-1643685 Disease 2 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
CCNB1CDK1LMNAMDM2PCNTPLK1PTTG1RAD21
Complex memberships
separase–CDK1–cyclin B1–CKS1 complexseparase–securin complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Yeast Esp1p (separase ortholog) forms a stable complex with the securin Pds1p; APC-mediated destruction of Pds1p liberates Esp1p, which is essential for dissociation of the cohesin Scc1p from sister chromatids at the metaphase-to-anaphase transition. Genetic epistasis, co-immunoprecipitation, yeast cell biology Cell High 9635435
1999 Vertebrate securin (PTTG) binds to the vertebrate separase homolog (Esp1/ESPL1 ortholog) and is degraded by the APC in a destruction-motif-dependent manner; expression of stable securin mutant blocks sister-chromatid separation without blocking cell cycle progression, establishing the securin–separase axis in vertebrates. Biochemical pulldown, cell-free Xenopus egg extract assays, stable mutant expression in mammalian cells Science High 10411507
1999 Yeast Pds1 (securin) blocks cyclin destruction and mitotic exit by inhibiting its binding partner Esp1; overexpression of Esp1 causes premature cyclin destruction and its effects depend on Cdc20 and mitotic-exit network components (Cdc5, Cdc14, Cdc15, Tem1). Genetic overexpression/deletion, cell-cycle synchronization assays Genes & development High 10444592
2001 Human separase (ESPL1) cleaves the cohesin subunit SCC1 at two defined sites; conditional expression of non-cleavable SCC1 in human cells blocks sister chromatid separation and also impairs cytokinesis, demonstrating that cohesin cleavage by separase is essential for both anaphase and cytokinesis. Site-directed mutagenesis of cleavage sites, conditional expression in human cells, cytological analysis Science High 11509732
2001 Separase is dually inhibited at metaphase: (1) by securin binding and (2) by CDC2 (CDK1)-dependent phosphorylation of a single site on separase that renders it inactive independently of securin; mutation of this phosphorylation site rescues sister-chromatid separation in extracts with high CDK1 activity, and quantitative mass spectrometry confirms complete phosphorylation at metaphase with dephosphorylation at anaphase. Xenopus egg extract reconstitution, site-directed mutagenesis, quantitative mass spectrometry Cell High 11747808
2001 Yeast Esp1 localizes to the spindle pole bodies and spindle midzone during anaphase B (tracked by live-cell imaging); association with Pds1 during S phase is required for efficient nuclear targeting of Esp1, and Pds1 also promotes Esp1 spindle binding; the conserved C-terminal domain of Esp1 is required for spindle interaction. Live-cell fluorescence imaging, NLS-fusion rescue, mutational analysis The Journal of cell biology High 11149918
2002 Human separase undergoes autocatalytic cleavage upon securin degradation; securin inhibits separase by blocking substrate access to the active site; the processed N- and C-terminal fragments remain associated and can be re-inhibited by securin; a non-cleavable separase mutant retains cohesin-cleavage activity in vitro. RNA interference, in vitro inhibitor binding assays, site-directed mutagenesis, immunoprecipitation Current biology High 12194817
2002 Phosphorylation of yeast securin Pds1 by Cdc28 (CDK1) promotes efficient binding of Pds1 to Esp1 and is required for efficient nuclear localization of Esp1, revealing a CDK1-dependent regulatory mechanism for the Pds1–Esp1 interaction. Kinase assays, co-immunoprecipitation, localization microscopy in yeast Genes & development High 12050115
2003 Full-length human separase cDNA was cloned; human separase localizes to mitotic spindle poles until anaphase onset, at which point it abruptly dissociates; autocatalytic processing occurs at anaphase entry and the cleavage sites were mapped by N-terminal sequencing and site-directed mutagenesis; separase depletion by antisense oligonucleotides causes high-fidelity chromosome segregation defects. cDNA cloning, immunofluorescence, N-terminal sequencing, site-directed mutagenesis, antisense knockdown Proceedings of the National Academy of Sciences High 12672959
2005 CDK1-cyclin B1 forms a stable complex with phosphorylated separase (second step of inhibition); complex formation inhibits both the separase protease and CDK1 kinase activities; vertebrate separase is a direct inhibitor of CDK1, and this function is negatively regulated by securin but independent of separase's proteolytic activity. In vitro kinase and protease assays, co-immunoprecipitation, mutagenesis Molecular cell High 15989971
2008 Yeast Esp1 protease activity is required for anaphase spindle elongation independently of its role in cleaving cohesin Mcd1; neither depletion nor ectopic cleavage of Mcd1 alone is sufficient for anaphase in esp1 temperature-sensitive mutants, indicating a second Esp1 protease substrate (likely spindle-associated) is needed for anaphase. Temperature-sensitive mutant analysis, ectopic TEV protease cleavage of Mcd1, genetic epistasis Genetics High 18430955
2008 Yeast Esp1 acts as a caspase-like protease during hydrogen peroxide-induced apoptosis, cleaving the cohesin subunit Mcd1; the C-terminal fragment of cleaved Mcd1 translocates from nucleus to mitochondria, causing decreased mitochondrial membrane potential and amplified cell death in a cytochrome c-dependent manner. Yeast apoptosis assay, subcellular fractionation, immunofluorescence, genetic deletion of ESP1 Molecular biology of the cell Medium 18321989
2008 Overexpression of mouse Separase in mammary epithelial cells induces premature chromatid separation, lagging chromosomes, anaphase bridges, aneuploidy, and tumorigenesis in vivo; Separase protein is significantly overexpressed in human breast tumors. Tetracycline-inducible conditional expression, in vivo mammary transplant model, cytogenetic analysis Proceedings of the National Academy of Sciences High 18728194
2009 Human separase (ESPL1) is required for centriole disengagement during mitotic exit; loss of separase blocks disengagement and delays new centriole assembly; Polo-like kinase 1 (Plk1) acts in parallel with separase to license centriole disengagement; combined loss of both separase and Plk1 completely abolishes disengagement and subsequent centriole duplication. RNAi knockdown in human cells, timed Plk1 inhibition, live-cell and fixed-cell imaging Developmental cell High 19758559
2012 Kendrin (pericentrin) is a novel separase substrate; separase cleaves kendrin at a consensus site in vivo and in vitro, leading to delayed release of kendrin from the centrosome in late mitosis; expression of non-cleavable kendrin suppresses centriole disengagement and subsequent centriole duplication. In vitro cleavage assay, in vivo cleavage site identification, non-cleavable mutant expression, centriole imaging Current biology High 22542101
2013 MMTV-Espl1 transgenic mice overexpressing separase in mammary glands develop aggressive, aneuploid, ERα-positive mammary adenocarcinomas with 80% penetrance; overexpression causes premature chromatid separation, centrosome amplification, DNA damage accumulation, and progressive loss of p53 and cadherin tumor suppressor loci. Transgenic mouse model, cytogenetics, histopathology, chromosomal instability assays Oncogene High 24276237
2015 Budding yeast Esp1 physically interacts with Ty1 retrotransposon integrase (identified by mass spectrometry and confirmed by co-immunoprecipitation); Esp1 promotes Ty1 retrotransposition by two mechanisms: removal of cohesin and targeting Ty1 integrase to chromatin; Securin/Pds1 is required for efficient nuclear localization of Esp1 and efficient Ty1 transposition. Genome-wide genetic interaction screens, mass spectrometry, co-immunoprecipitation, transposition mobility assays PLoS genetics Medium 25822502
2016 c-MYB transcription factor binds to the ESPL1 promoter and positively regulates separase expression in CML cells; imatinib treatment reduces c-MYB levels and correlates with reduced separase protein levels; RNA silencing of c-MYB reduces separase protein levels. ChIP assay, gel-shift assay, RNAi, qRT-PCR, western blot Biomarker research Medium 26937281
2018 Cdk1 phosphorylates yeast Esp1/separase to activate it at anaphase onset; this activation is opposed by PP2A-Cdc55 and the spindle protein Slk19; phospho-mimetic mutations in ESP1 combined with Pds1 degradation cause premature anaphase spindle elongation, disruption of pericentric cohesin organization, and chromosome mis-segregation. Phospho-mimetic and phospho-null mutations, genetic epistasis, live-cell imaging, chromosome segregation assays PLoS genetics High 29561844
2021 Cryo-EM structures of human separase in complex with securin or CDK1-cyclin B1-CKS1 reveal the molecular basis of dual inhibition: securin uses pseudosubstrate motifs to block substrate binding at the active site and adjacent docking sites; CDK1-cyclin B1 deploys pseudosubstrate motifs from intrinsically disordered loops in separase itself, including an autoinhibitory loop that blocks CDK1's own active site, and a phosphoserine on separase that binds a conserved pocket in cyclin B1 to stabilize the complex. Cryo-electron microscopy structure determination, structural analysis of inhibitory complexes Nature High 34290405
2024 ESPL1 interacts with MDM2, an E3 ubiquitin ligase, in gastric cancer cells (identified by CRISPR gain-of-function screen and confirmed by co-immunoprecipitation); ESPL1 inhibition suppresses cell proliferation and migration; combined MDM2 siRNA with apatinib synergistically reverses ESPL1-mediated drug resistance. CRISPR genome-wide gain-of-function screen, co-immunoprecipitation, RNAi knockdown, proliferation/migration assays Cancer cell international Medium 38402402
2025 BRD4 serves as a scaffold for ubiquitin enzyme TRIM21 and the m6A demethylase ALKBH5, leading to ubiquitination and degradation of ALKBH5; BRD4 inhibition (JQ1) increases ALKBH5 levels, which demethylates ESPL1 mRNA, reducing its binding to the m6A reader IGF2BP3 and causing ESPL1 mRNA decay, thereby suppressing breast cancer malignancy. siRNA/inhibitor treatment, RIP assay, m6A sequencing, co-immunoprecipitation, ubiquitination assay, animal models Acta pharmaceutica Sinica. B Medium 40370540
2025 Drosophila separase (Sse) and human ESPL1 both physically interact with nuclear lamins (lamin C/Dm0 in flies; lamin A in human fibroblasts) and colocalize at the nuclear envelope during interphase; loss of separase increases lamin A levels and causes misshapen nuclei and impaired locomotion in flies, revealing an evolutionarily conserved role for separase in nuclear lamin regulation. Co-immunoprecipitation in flies and human cells, immunofluorescence co-localization, proteomics, RNAi depletion in human fibroblasts bioRxivpreprint Medium
2025 PAX2 transcriptionally activates ESPL1 by binding its promoter; ESPL1 overexpression activates the JAK2/STAT3 signaling pathway to promote cisplatin resistance in bladder cancer; silencing ESPL1 restores cisplatin sensitivity and inhibits tumor growth in xenograft models. ChIP assay, luciferase reporter assay, siRNA/overexpression, JAK2 inhibitor (AG490), xenograft model Naunyn-Schmiedeberg's archives of pharmacology Medium 38573552

Source papers

Stage 0 corpus · 78 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1999 Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science (New York, N.Y.) 667 10411507
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1998 An ESP1/PDS1 complex regulates loss of sister chromatid cohesion at the metaphase to anaphase transition in yeast. Cell 520 9635435
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2001 Cohesin cleavage by separase required for anaphase and cytokinesis in human cells. Science (New York, N.Y.) 419 11509732
2001 Dual inhibition of sister chromatid separation at metaphase. Cell 383 11747808
2005 Dissociation of cohesin from chromosome arms and loss of arm cohesion during early mitosis depends on phosphorylation of SA2. PLoS biology 366 15737063
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 The male mouse pheromone ESP1 enhances female sexual receptive behaviour through a specific vomeronasal receptor. Nature 269 20596023
2009 Polo kinase and separase regulate the mitotic licensing of centriole duplication in human cells. Developmental cell 243 19758559
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2015 A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning. eLife 198 26673895
2009 SEPA-1 mediates the specific recognition and degradation of P granule components by autophagy in C. elegans. Cell 198 19167332
2002 Regulation of human separase by securin binding and autocleavage. Current biology : CB 179 12194817
2005 Mutual inhibition of separase and Cdk1 by two-step complex formation. Molecular cell 171 15989971
1995 SepA, the major extracellular protein of Shigella flexneri: autonomous secretion and involvement in tissue invasion. Molecular microbiology 154 7476198
2020 A High-Density Human Mitochondrial Proximity Interaction Network. Cell metabolism 148 32877691
1999 Pds1 and Esp1 control both anaphase and mitotic exit in normal cells and after DNA damage. Genes & development 142 10444592
1990 The fission yeast cut1+ gene regulates spindle pole body duplication and has homology to the budding yeast ESP1 gene. Cell 137 2203537
2001 A novel role of the budding yeast separin Esp1 in anaphase spindle elongation: evidence that proper spindle association of Esp1 is regulated by Pds1. The Journal of cell biology 130 11149918
2008 Overexpression of Separase induces aneuploidy and mammary tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America 126 18728194
2002 Functional characterization and localization of the Aspergillus nidulans formin SEPA. Molecular biology of the cell 125 11854405
1996 Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1. DNA research : an international journal for rapid publication of reports on genes and genomes 114 8724849
1997 The Aspergillus nidulans sepA gene encodes an FH1/2 protein involved in cytokinesis and the maintenance of cellular polarity. The EMBO journal 108 9218790
1992 Requirement for ESP1 in the nuclear division of Saccharomyces cerevisiae. Molecular biology of the cell 102 1493337
2018 Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. Molecular & cellular proteomics : MCP 101 30021884
2012 Kendrin is a novel substrate for separase involved in the licensing of centriole duplication. Current biology : CB 100 22542101
2007 The complete removal of cohesin from chromosome arms depends on separase. Journal of cell science 79 18003702
2003 Processing, localization, and requirement of human separase for normal anaphase progression. Proceedings of the National Academy of Sciences of the United States of America 77 12672959
2021 Structural basis of human separase regulation by securin and CDK1-cyclin B1. Nature 71 34290405
2019 MAD1-dependent recruitment of CDK1-CCNB1 to kinetochores promotes spindle checkpoint signaling. The Journal of cell biology 71 30674583
2002 Phosphorylation of the mitotic regulator Pds1/securin by Cdc28 is required for efficient nuclear localization of Esp1/separase. Genes & development 68 12050115
2013 MMTV-Espl1 transgenic mice develop aneuploid, estrogen receptor alpha (ERα)-positive mammary adenocarcinomas. Oncogene 56 24276237
2008 Cleavage of Mcd1 by caspase-like protease Esp1 promotes apoptosis in budding yeast. Molecular biology of the cell 50 18321989
2017 The metalloprotease SepA governs processing of accumulation-associated protein and shapes intercellular adhesive surface properties in Staphylococcus epidermidis. Molecular microbiology 45 27997732
2017 Shigella depends on SepA to destabilize the intestinal epithelial integrity via cofilin activation. Gut microbes 45 28598765
2014 ESPL1 is a candidate oncogene of luminal B breast cancers. Breast cancer research and treatment 43 25086634
1998 SepA, the 110 kDa protein secreted by Shigella flexneri: two-domain structure and proteolytic activity. Microbiology (Reading, England) 43 9695914
2016 Self-Exposure to the Male Pheromone ESP1 Enhances Male Aggressiveness in Mice. Current biology : CB 34 27151664
1998 Cloning and tissue distribution of a novel serine protease esp-1 from human eosinophils. Biochemical and biophysical research communications 31 9826525
2008 The protease activity of yeast separase (esp1) is required for anaphase spindle elongation independently of its role in cleavage of cohesin. Genetics 28 18430955
1996 Human ESP1/CRP2, a member of the LIM domain protein family: characterization of the cDNA and assignment of the gene locus to chromosome 14q32.3. Genomics 28 8824798
2022 SEPA: signaling entropy-based algorithm to evaluate personalized pathway activation for survival analysis on pan-cancer data. Bioinformatics (Oxford, England) 26 35199150
2006 Pds1/Esp1-dependent and -independent sister chromatid separation in mutants defective for protein phosphatase 2A. Proceedings of the National Academy of Sciences of the United States of America 25 17050679
2019 Quercetin a major biomarker of Psidium guajava L. inhibits SepA protease activity of Shigella flexneri in treatment of infectious diarrhoea. Microbial pathogenesis 23 31629796
1999 Structural analysis of esp-1 gene (PRSS 21). Biochemical and biophysical research communications 20 10600542
2020 High Rate of Detection of Human ESPL1-HBV S Fusion Gene in Patients With HBV-related Liver Cancer: A Chinese Case-Control Study. Anticancer research 15 31892573
2018 Cdk1 phosphorylation of Esp1/Separase functions with PP2A and Slk19 to regulate pericentric Cohesin and anaphase onset. PLoS genetics 15 29561844
2009 The STE group kinase SepA controls cleavage furrow formation in Dictyostelium. Cell motility and the cytoskeleton 15 19479821
2011 Genetic analysis of cysteine-poor prolamin polypeptides reduced in the endosperm of the rice esp1 mutant. Plant science : an international journal of experimental plant biology 14 21683877
2015 A role for the budding yeast separase, Esp1, in Ty1 element retrotransposition. PLoS genetics 13 25822502
2013 Structure of the mouse sex peptide pheromone ESP1 reveals a molecular basis for specific binding to the class C G-protein-coupled vomeronasal receptor. The Journal of biological chemistry 13 23576433
2012 The Arabidopsis CstF64-Like RSR1/ESP1 Protein Participates in Glucose Signaling and Flowering Time Control. Frontiers in plant science 13 22629280
2021 SepA Enhances Shigella Invasion of Epithelial Cells by Degrading Alpha-1 Antitrypsin and Producing a Neutrophil Chemoattractant. mBio 11 34724811
2023 Pan-Cancer analysis and experimental validation identify the oncogenic nature of ESPL1: Potential therapeutic target in colorectal cancer. Frontiers in immunology 10 37006282
2020 Serum ESPL1 Can Be Used as a Biomarker for Patients With Hepatitis B Virus-Related Liver Cancer: A Chinese Case-Control Study. Technology in cancer research & treatment 10 33308056
2016 c-MYB is a transcriptional regulator of ESPL1/Separase in BCR-ABL-positive chronic myeloid leukemia. Biomarker research 10 26937281
2024 Genome-wide CRISPR screen identifies ESPL1 limits the response of gastric cancer cells to apatinib. Cancer cell international 9 38402402
2024 PAX2 mediated upregulation of ESPL1 contributes to cisplatin resistance in bladder cancer through activating the JAK2/STAT3 pathway. Naunyn-Schmiedeberg's archives of pharmacology 7 38573552
2025 BRD4 regulates m6A of ESPL1 mRNA via interaction with ALKBH5 to modulate breast cancer progression. Acta pharmaceutica Sinica. B 6 40370540
2022 Let-7c-5p Restrains Cell Growth and Induces Apoptosis of Lung Adenocarcinoma Cells via Targeting ESPL1. Molecular biotechnology 6 35639278
2023 Correlation Between Serum ESPL1 and Hepatitis B Virus-related Hepatocellular Carcinoma Histological Grade: A Chinese Single-center Case-control Study. Anticancer research 5 37648308
2018 Aspergillus nidulans protein kinase C forms a complex with the formin SepA that is involved in apical growth and septation. Fungal genetics and biology : FG & B 4 30391723
2025 Evaluation of serum ESPL1 as a biomarker for early diagnosis of HBV-related hepatocellular carcinoma. Frontiers in oncology 3 40248196
1999 R-esp1, a rat homologue of drosophila groucho, is differentially expressed after optic nerve crush and mediates NGF-induced survival of PC12 cells. FEBS letters 3 10471788
2025 Polyploid Formation Through Disrupting Mitotic Sister Chromatid Separation of Spermatogonia based on espl1 Heterozygous Knockout in Fish. Molecular biology and evolution 1 40794720
2025 Bioinformatics insights into TMPO-AS1-let-7b-5p-ESPL1/E2F8 regulatory axis in breast cancer. Frontiers in cell and developmental biology 0 41268575
2024 The Saccharomyces cerevisiae cell lysis mutant cly8 is a temperature-sensitive allele of ESP1. bioRxiv : the preprint server for biology 0 39484378
2005 Mechanisms of SEPA 0009-induced tumorigenesis in v-rasHa transgenic Tg.AC mice. Toxicologic pathology 0 16176921