Affinage

PTTG1

Securin · UniProt O95997

Length
202 aa
Mass
22.0 kDa
Annotated
2026-06-10
100 papers in source corpus 44 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTTG1 (securin) is a natively disordered protein that operates as the principal regulator of sister-chromatid separation while doubling as a transforming oncogene that rewires transcriptional and signaling programs (PMID:9092795, PMID:15929994). In its canonical mitotic role, PTTG1 inhibits separase by binding as a pseudo-substrate that occludes the catalytic and docking sites, as resolved by cryo-EM of the human separase–securin complex (PMID:34290405); timely anaphase requires its destruction, which is achieved by APC/C-Cdc20 and APC/C-Cdh1 acting through an RXXL destruction box and a KEN box, with non-degradable securin causing incomplete chromatid separation (PMID:11179223). Genetic epistasis in yeast establishes securin (with B-cyclin/CDK) as one of the two obligate APC/C substrates that explain APC essentiality (PMID:14634663), and an alternative SGO2-MAD2 pseudo-substrate inhibitor can functionally replace securin, revealing redundant control of separase (PMID:32322060). PTTG1 protein peaks in mitosis and is phosphorylated by CDK1 (PMID:10656688), while GSK-3β phosphorylation routes it for SCF(βTrCP)-mediated degradation during interphase and after UV damage via a DDAYPE motif (PMID:18460583, PMID:21757741); consistent with a damage-surveillance link, PTTG1 binds the Ku/DNA-PK complex and is phosphorylated by DNA-PK, an association disrupted by DNA double-strand breaks (PMID:11238996). Dysregulated PTTG1 is directly oncogenic and a driver of chromosomal instability (PMID:9092795, PMID:15897900), activities that depend on C-terminal PXXP/SH3-binding motifs and a C-terminal transactivation domain required for transformation, tumorigenesis, and induction of secreted factors including bFGF, VEGF, IL-8, MMP-2, and galectin-1 (PMID:9892021, PMID:10713046, PMID:15649325, PMID:19351864, PMID:17096843). PTTG1 suppresses tumor-suppressive programs by binding p53 to block its DNA binding and pro-apoptotic transcription (PMID:12355087) and by restraining p21-dependent senescence upstream of the p21/Rb axis (PMID:15919720, PMID:21858218). Beyond mitosis, PTTG1 associates with Golgi-resident microtubule nucleation machinery (GM130, AKAP450, γ-tubulin) to control microtubule nucleation, cell polarity, and directional migration (PMID:21937724), and stabilizes β-catenin by competing with GSK3β for PP2A binding to sustain Wnt signaling (PMID:37400529). Its expression is driven by a convergent transcriptional network including E2F1 (downstream of Rb inactivation), STAT3, FoxM1, Sp1/NF-Y, and p300-mediated histone acetylation (PMID:14644503, PMID:19837943, PMID:19539243, PMID:23416975, PMID:26264222).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1997 Medium

    Established that PTTG is a transforming oncogene rather than a passive cell-cycle component, motivating mechanistic dissection of its oncogenic activity.

    Evidence Stable transfection of NIH 3T3 fibroblasts with soft-agar transformation and nude-mouse tumor assays

    PMID:9092795

    Open questions at the time
    • Did not define the molecular domain or partner responsible for transformation
    • Single lab, single cell background
  2. 1999 High

    Mapped oncogenic activity to C-terminal PXXP SH3-binding motifs, defining a structural determinant of transformation and growth-factor induction.

    Evidence Site-directed mutagenesis of PXXP prolines with transformation, tumorigenesis, and bFGF secretion readouts

    PMID:9892021

    Open questions at the time
    • SH3-domain partner protein not identified
    • Mechanistic link between PXXP motifs and growth-factor secretion unresolved
  3. 2000 High

    Defined PTTG as a transactivator whose acidic/proline-rich C-terminus drives transcription in a manner tied to its transforming capacity, and identified CDK1 as the mitotic kinase phosphorylating it.

    Evidence Transactivation reporter assays in yeast and mammalian cells, mutagenesis, immunodepletion plus in vitro phosphorylation with CDK1 inhibitor

    PMID:10656688 PMID:10713046 PMID:9811450

    Open questions at the time
    • Direct transcriptional target genes not identified at this stage
    • Functional consequence of CDK1 phosphorylation site unmapped
  4. 2001 High

    Established the canonical mitotic mechanism: APC/C-Cdc20/Cdh1 degrades securin via RXXL and KEN box motifs to permit chromatid separation, and connected PTTG to DNA-damage sensing through Ku/DNA-PK.

    Evidence In vitro ubiquitination reconstitution with fzy/fzr, non-degradable securin phenotype, plus reciprocal Co-IP and in vitro kinase assay with DNA-PK

    PMID:11179223 PMID:11238996

    Open questions at the time
    • The separase-inhibitory mechanism was not yet structurally defined
    • Physiological role of DNA-PK phosphorylation of PTTG unresolved
  5. 2002 High

    Identified p53 as a direct PTTG1 partner, providing a route by which oncogenic PTTG1 suppresses apoptosis and transcription.

    Evidence Phage display, reciprocal pull-down/Co-IP, reporter and apoptosis assays in PTTG1-/- cells

    PMID:12355087

    Open questions at the time
    • Biophysical study later found no interaction between unmodified recombinant securin and p53, implying a modification- or cofactor-dependent interaction not yet defined
  6. 2003 High

    Generalized securin as one of only two obligate APC/C substrates, explaining why the APC is essential, and extended PTTG transcriptional control to endocrine genes.

    Evidence Systematic genetic epistasis across essential APC subunits in S. cerevisiae; GH3 prolactin promoter reporter with PXXP mutagenesis

    PMID:12554778 PMID:14634663

    Open questions at the time
    • Yeast bypass does not address metazoan-specific APC functions
    • Mechanism of PRL promoter repression by the PXXP motif unresolved
  7. 2005 High

    Resolved that securin is intrinsically disordered and placed PTTG genetically upstream of the p21/Rb cell-cycle and chromosomal-instability axis.

    Evidence Multi-method biophysics (NMR, CD, AUC); shRNA in corticotrophs with Pttg-/-×Rb+/- crosses; FISSR-PCR genomic instability assay

    PMID:15897900 PMID:15919720 PMID:15929994

    Open questions at the time
    • Disordered state complicates structural rationalization of partner binding
    • Causal chain from PTTG to genomic instability mechanistically incomplete
  8. 2008 High

    Defined an interphase, separase-independent degradation route in which GSK-3β-primed SCF(βTrCP) targets securin via a DDAYPE motif, especially after UV damage.

    Evidence In vivo ubiquitination, βTrCP/CUL1 co-expression and knockdown, GSK-3β inhibitors, motif identification

    PMID:18460583

    Open questions at the time
    • Physiological signals coupling GSK-3β to securin outside UV stress not fully defined
  9. 2009 High

    Built the upstream transcriptional and post-translational regulatory network of PTTG (E2F1/Rb, p300/HAT, viral HBx stabilization) and extended its functions to senescence and differentiation control.

    Evidence ChIP and pull-down for E2F1; ChIP for H3 acetylation by p300; in vitro ubiquitination/Co-IP for HBx; Pttg-/-×p21-/- crosses; Dlk1 mRNA-stability and adipogenesis assays

    PMID:19213844 PMID:19539243 PMID:19837943 PMID:20198633

    Open questions at the time
    • Hierarchy among the multiple transcriptional inputs unresolved
    • Mechanism of HBx-mediated SCF disruption not structurally defined
  10. 2011 High

    Expanded PTTG1 into non-mitotic territory: Golgi-associated microtubule nucleation and migration, membrane-traffic/endosomal control with separase, and GSK3β-driven SCF(βTrCP) turnover linked to breast cancer.

    Evidence Co-IP/colocalization and RNAi migration assays for GM130/AKAP450/γ-tubulin; siRNA secretion/recycling/acidification assays; in vitro kinase and ubiquitination assays with tissue correlation

    PMID:21272169 PMID:21757741 PMID:21937724

    Open questions at the time
    • How a securin pool is partitioned to the Golgi versus the spindle is unclear
    • Direct enzymatic versus scaffolding contribution to microtubule nucleation undefined
  11. 2013 High

    Positioned PTTG1 as a downstream effector of oncogenic transcription factors (STAT3, FoxM1) and metastatic secretory programs (galectin-1/c-Myc, MMP-2, integrin-αV/FAK).

    Evidence ChIP, reporter assays, siRNA epistasis and in vivo metastasis models across colorectal, esophageal, and lung cancer systems

    PMID:17096843 PMID:19351864 PMID:22081074 PMID:23416975 PMID:26264222

    Open questions at the time
    • Whether these effects require nuclear PTTG1, the PXXP motif, or partner recruitment is not uniformly resolved
  12. 2021 High

    Provided the high-resolution structural mechanism of separase inhibition and showed securin is functionally redundant with SGO2-MAD2.

    Evidence Cryo-EM of human separase–securin and separase–CDK1–cyclinB1–CKS1 complexes; in vitro separase liberation and securin/SGO2 co-depletion epistasis

    PMID:32322060 PMID:34290405

    Open questions at the time
    • Structural basis of PTTG1's non-mitotic interactions (p53, β-catenin, Golgi complex) not addressed
  13. 2023 Medium

    Defined new oncogenic mechanisms: β-catenin stabilization through PP2A competition with GSK3β, and metabolic reprogramming via ASNS-driven asparagine/mTOR signaling.

    Evidence Co-IP, phospho-mutant and PP2A-inhibitor analysis; in vivo HCC models with ChIP, metabolomics, and asparaginase rescue

    PMID:37159932 PMID:37400529

    Open questions at the time
    • Single-lab findings without independent replication
    • Integration of metabolic, Wnt, and mitotic roles within one cell undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PTTG1's intrinsically disordered structure encodes its diverse, mutually exclusive interactions and how its subcellular partitioning (spindle, Golgi, nucleus) is governed remain unresolved.
  • No unifying structural model for non-separase partners
  • Determinants directing PTTG1 between mitotic, migratory, and transcriptional pools unknown
  • Reconciliation of in-cell p53 binding with negative in vitro biophysics outstanding

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0060090 molecular adaptor activity 2 GO:0140313 molecular sequestering activity 2
Localization
GO:0005634 nucleus 2 GO:0005794 Golgi apparatus 2 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-162582 Signal Transduction 2 R-HSA-73894 DNA Repair 2
Partners
CTNNB1ESPL1GM130GSK3BPPP2CAPRKDCTP53XRCC6
Complex memberships
Golgi microtubule nucleation complex (GM130/AKAP450/γ-tubulin)separase-securin complex

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Overexpression of PTTG in mouse 3T3 fibroblasts inhibits cell proliferation and induces cell transformation in vitro; injection of transfected cells into athymic nude mice resulted in tumor formation, establishing PTTG as a transforming oncogene. Stable transfection of NIH 3T3 fibroblasts, soft-agar transformation assay, nude mouse tumor formation assay Molecular endocrinology Medium 9092795
1999 Human PTTG protein contains two C-terminal PXXP motifs that serve as SH3-domain binding sites; site-directed mutagenesis of these proline residues abrogates PTTG in vitro transforming activity, in vivo tumor-inducing activity, and stimulation of bFGF secretion. Site-directed mutagenesis of PXXP motifs, NIH 3T3 transformation assay, nude mouse tumor assay, bFGF secretion measurement Molecular endocrinology High 9892021
1998 hPTTG is mainly a cytosolic protein with partial nuclear localization; its acidic C-terminal domain acts as a transcriptional transactivation domain when fused to a heterologous DNA-binding domain, active in both yeast and mammalian cells. Subcellular fractionation, transactivation reporter assay (yeast and mammalian cells) Oncogene Medium 9811450
2000 hPTTG protein level peaks in mitosis and is phosphorylated during mitosis; immunodepletion and in vitro phosphorylation experiments with a specific inhibitor identified Cdc2 (CDK1) as the kinase that phosphorylates hPTTG. Cell cycle synchronization, immunodepletion, in vitro phosphorylation assay, CDK1 inhibitor treatment Oncogene High 10656688
2000 Murine PTTG possesses transcriptional transactivation activity that correlates with its transforming properties; Pro139, Ser159, PPXP motif, and a hydrophobic stretch are required for transactivation, and Ala substitution at Pro139 abolishes both transactivation and transformation. Transactivation reporter assay, site-directed mutagenesis, NIH 3T3 transformation assay The Journal of biological chemistry High 10713046
2000 PTTG-EGFP colocalizes with mitotic spindles in early mitosis and is degraded at anaphase; overexpression of wild-type PTTG-EGFP causes most cells to die by apoptosis, while a mutant PTTG-EGFP lacking the SH3-binding domain allows cell division, demonstrating that PTTG regulates endocrine tumor cell division and survival in a PXXP-dependent manner. Live-cell imaging of EGFP-PTTG conjugates, real-time fluorescence microscopy of cell cycle progression Molecular endocrinology Medium 10935539
2001 Human securin/PTTG degradation is catalyzed by both fzy (Cdc20) and fzr (Cdh1) APC/C activators via an RXXL destruction box and a KEN box; non-degradable securin (both sequences mutated) causes incomplete chromatid separation but does not prevent cytokinesis. In vitro ubiquitination assay with fzy/fzr, expression of non-degradable securin mutant in cells, mitotic phenotype analysis The EMBO journal High 11179223
2001 hPTTG binds to Ku heterodimer (the regulatory subunit of DNA-PK) both in vitro and in vivo; DNA-PK catalytic subunit phosphorylates hPTTG in vitro; DNA double-strand breaks prevent hPTTG–Ku association, suggesting PTTG connects DNA-damage response to sister chromatid separation. Co-immunoprecipitation (in vivo), in vitro binding assay (pull-down), in vitro kinase assay, DNA damage induction Nucleic acids research High 11238996
2002 Human securin/PTTG1 interacts directly with p53 (demonstrated by pull-down and co-IP both in vitro and in vivo); this interaction blocks p53 binding to DNA, inhibits p53 transcriptional activity, and inhibits p53-induced cell death; PTTG1-deficient cells show potentiated p53 apoptotic and transactivating functions. Phage-display screening, pull-down assay, co-immunoprecipitation, transcriptional reporter assay, apoptosis assay in PTTG1-/- cells Nature genetics High 12355087
2003 Securin and B-cyclin/CDK are the only obligatory APC/C targets in S. cerevisiae; simultaneous removal of securin (Pds1) and B-cyclin/CDK renders all eight essential APC subunits dispensable, establishing that these two substrates explain APC essentiality. Genetic epistasis in S. cerevisiae — double-deletion/bypass suppression of APC subunit mutations by simultaneous removal of Pds1 (securin) and Clb/CDK Nature cell biology High 14634663
2003 PTTG/securin represses prolactin (PRL) promoter activity and mRNA/protein expression via its intact C-terminal PPSP motif; mutation of the PXXP motif abolishes this repression; estrogen partially rescues PRL expression in PTTG C-terminus transfectants. Stable transfection in GH3 cells, PRL promoter luciferase assay, Northern/Western blot, site-directed mutagenesis of PXXP motif Molecular endocrinology Medium 12554778
2003 Sp1 and NF-Y transcription factors bind within nucleotides –540 to –500 of the PTTG promoter in vivo; mutation of the Sp1 consensus reduces PTTG promoter activity by ~70%, and combined Sp1+NF-Y mutation causes ~90% loss, identifying Sp1 as the primary transcriptional regulator of PTTG. 5' RACE, deletion analysis, EMSA, chromatin immunoprecipitation (ChIP), site-directed mutagenesis, luciferase reporter assay Gene High 14644503
2005 Human full-length Securin is a natively unfolded/intrinsically disordered protein lacking tertiary and secondary structure under physiological conditions, with only a small poly-(L-proline) type II helix; analytical ultracentrifugation and fluorescence anisotropy detected no direct interaction between unmodified recombinant Securin and p53 in vitro. NMR, circular dichroism, size-exclusion chromatography, analytical ultracentrifugation, fluorescence anisotropy Protein science High 15929994
2005 Pttg silencing in AtT20 corticotrophs markedly induces p21 mRNA/protein, decreases Rb phosphorylation, and reduces S-phase cells by 24%; Pttg-null mice have pituitary hypoplasia and Rb+/-Pttg-/- double-knockout mice show dramatically reduced pituitary tumor incidence (30% vs. 86%), placing PTTG upstream of p21/Rb in the pituitary cell cycle pathway. shRNA knockdown in AtT20 cells, p21/Rb Western blot, BrdU S-phase measurement, Pttg-/- × Rb+/- genetic cross, tumor incidence analysis Molecular endocrinology High 15919720
2005 PTTG overexpression induces genetic instability in thyroid follicular cells (FTC133) in a dose-dependent manner; PTTG expression correlates with genomic instability index in thyroid cancers in vivo, establishing PTTG as a direct inducer of chromosomal instability. FISSR-PCR genomic instability assay, PTTG transfection into FTC133 cells at different doses, correlation analysis in cancer tissue Oncogene Medium 15897900
2005 Ectopic PTTG1 expression in human HEK293 cells promotes tumorigenesis through increased secretion/expression of bFGF, VEGF, and IL-8; mutation of C-terminal proline-rich (PXXP) motifs abolishes oncogenic properties and growth factor induction. Stable transfection of HEK293 cells, soft-agar colony formation, nude mouse tumor assay, ELISA/RT-PCR for growth factors, PXXP site-directed mutagenesis Molecular cancer Medium 15649325
2004 PTTG C-terminal PXXP motif phosphorylation status independently controls cell proliferation (phosphorylation inhibits transformation; phosphomimetic mutants reduce proliferation) and transactivation of FGF-2 requires intact PXXP but not phosphorylation; live-cell imaging shows PTTG mitotic regulation is independent of phosphorylation. Live-cell imaging of EGFP-PTTG, colony-formation assay, [3H]thymidine incorporation, FGF-2 transactivation in primary thyroid and PTTG-null cells, site-directed mutagenesis Journal of molecular endocrinology Medium 15591026
2007 PTTG and its binding factor PBF repress sodium iodide symporter (NIS) mRNA expression and iodide uptake; repression is mediated through the NIS upstream enhancer element (hNUE) via a PAX8-USF1 response element, with PTTG repression specifically dependent on the USF1 site; FGF-2 mediates this process at least in part. NIS promoter luciferase assay (deletion/mutation analysis), iodide uptake assay in FRTL-5 cells, primary human thyroid cells Oncogene Medium 17297475
2008 UV radiation induces securin degradation via the SCF(βTrCP) E3 ubiquitin ligase; GSK-3β inhibitors prevent UV-induced securin degradation; βTrCP recognizes a conserved unconventional motif (DDAYPE) in securin; βTrCP knockdown causes securin accumulation even in non-irradiated cells. In vivo ubiquitination assay, CUL1/βTrCP co-expression/knockdown, GSK-3β inhibitor treatment, UV irradiation, identification of βTrCP recognition motif Journal of cell science High 18460583
2009 E2F1 directly binds the hPTTG1 promoter and transactivates PTTG1 expression; Rb inactivation by siRNA concordantly elevates E2F1 and PTTG1; endogenous p53/p21 constrains E2F1-induced PTTG1 transactivation; E2F1 and PTTG1 are concordantly overexpressed in Rb+/- murine and human pituitary tumors. ChIP, biotin-streptavidin pull-down assay, luciferase reporter assay, E2F1/DP1 co-transfection, siRNA knockdown of Rb/p53/p21 Molecular endocrinology High 19837943
2009 PTTG overexpression induces Dlk1 expression by promoting stability/accumulation of Dlk1 mRNA (posttranscriptional regulation); PTTG overexpression inhibits adipogenesis in 3T3-L1 cells and this is accomplished through Dlk1. Inducible PTTG expression cell lines, differential display, Dlk1 mRNA stability assay, adipogenesis assay in 3T3-L1 cells Molecular biology of the cell Medium 19477929
2009 HBx protein promotes accumulation of PTTG1 protein (without affecting mRNA) by inhibiting PTTG1 ubiquitination and disrupting its interaction with the SCF ubiquitin ligase complex; HBx co-localizes with PTTG1 and Cul1 by confocal microscopy. In vitro ubiquitination assay, GST pull-down, co-immunoprecipitation, confocal microscopy, HBx transgenic mouse liver and patient biopsies Hepatology High 20198633
2009 Histone acetyltransferase p300 upregulates hPTTG expression at the level of promoter activity, mRNA, and protein; p300 HAT activity is required; p300 overexpression elevates histone H3 acetylation at the hPTTG promoter (by ChIP); NF-Y sites at the promoter synergize with p300; HDAC3 decreases and the HDAC inhibitor TSA increases hPTTG promoter activity. Luciferase reporter assay, ChIP for histone H3 acetylation, HDAC3 overexpression, TSA treatment, Western/RT-PCR Journal of genetics and genomics Medium 19539243
2009 PTTG deletion in mice causes beta-cell apoptosis and senescence (SA-β-gal activity) associated with progressive p21 upregulation and DNA damage; p21 deletion partially rescues PTTG-/- mice from diabetes, placing PTTG upstream of p21-dependent senescence in pancreatic beta cells. PTTG-/- mouse model, p21-/- × PTTG-/- genetic cross, SA-β-gal staining, apoptosis assay, p21 Western blot, DNA damage gene array Endocrinology High 19213844
2011 A portion of cytoplasmic PTTG1 associates with the cis face of the Golgi apparatus in a phosphorylation-dependent manner; PTTG1 forms a complex with microtubule nucleation proteins GM130, AKAP450, and γ-tubulin at the Golgi; RNAi depletion of PTTG1 delays centrosomal and non-centrosomal microtubule nucleation and causes severe defects in cell polarization and directional migration. Subcellular fractionation, immunofluorescence colocalization, co-immunoprecipitation, RNAi knockdown, wound-healing/migration assay, microtubule regrowth assay Molecular biology of the cell High 21937724
2011 GSK3β phosphorylates securin/PTTG1 to promote its proteolysis via SCF(βTrCP) E3 ubiquitin ligase; GSK3β inactivation correlates with securin accumulation in human breast cancer tissues. In vitro kinase assay, ubiquitination assay, GSK3β inhibitor treatment, correlation analysis in breast cancer tissue specimens The Journal of biological chemistry High 21757741
2011 Securin and separase associate with membranes and their depletion causes trans-Golgi network swelling, appearance of large perinuclear endocytic vesicles, diminished constitutive protein secretion, impaired receptor recycling/degradation, and defective acidification of early endosomes with increased V-ATPase membrane recruitment. siRNA depletion of securin/separase, fluorescence microscopy, secretion assays, receptor recycling/degradation assays, endosomal pH measurement, V-ATPase localization Traffic Medium 21272169
2011 PTTG promotes lymph node metastasis in esophageal squamous cell carcinoma by upregulating S100A4 and galectin-1 secretion and downregulating TIMP-2; PTTG activates E-box transcription and induces c-Myc protein, which then binds the galectin-1 promoter (confirmed by ChIP); galectin-1 siRNA constrains PTTG-induced cell motility. Mass spectrometric analysis of conditioned media, Western blot, RT-PCR, ChIP assay for c-Myc binding to galectin-1 promoter, siRNA knockdown, in vivo lymph node metastasis model Cancer research High 19351864
2012 A single point mutation T60A in securin/PTTG1 enhances its oncogenic properties, inducing chromosomal instability (by FACS and FISH) and increased cell invasion. Site-directed mutagenesis, FACS cell cycle analysis, FISH for aneuploidy, tumor cell migration/invasion assays, gene expression microarray European journal of cancer Medium 22819078
2013 STAT3 directly binds the human PTTG promoter and induces PTTG transcriptional activity; STAT3-induced cell growth, colony formation, migration and invasion in colorectal cancer cells require PTTG; STAT3 and PTTG are concordantly expressed in human colorectal tumors. ChIP assay, luciferase reporter assay, STAT3/STAT3-C/STAT3-DN transfection, PTTG siRNA knockdown, in vivo tumor xenograft, nude mouse metastasis model Oncogene High 23416975
2015 FoxM1 directly binds the PTTG1 promoter at the –391 to –385 bp region and transactivates PTTG1 expression; FoxM1-PTTG1 pathway promotes colorectal cancer cell migration, invasion, and liver metastasis in vivo; PTTG1 suppresses DKK1, a WNT pathway inhibitor. Luciferase reporter assay, EMSA, ChIP assay, Boyden chamber migration/invasion assay, splenic injection liver metastasis model, Illumina microarray BMC medical genomics High 26264222
2011 PTTG induces EMT in lung cancer cells through upregulation of integrin αVβ3 and activation of FAK; downstream adhesion complex molecules (paxillin, metavincullin, talin) and Rho GTPases (Rac1, RhoA, Cdc42, DOCK180) are upregulated; blockade of integrin αV by echistatin or siRNA abolishes FAK activation and subsequent actin cytoskeleton disruption. Adenoviral PTTG overexpression/siRNA knockdown, Western blot, integrin αV antagonist (echistatin), αV-specific siRNA, actin cytoskeleton staining, cell motility assay Oncogene Medium 22081074
2006 PTTG overexpression induces MMP-2 secretion and expression (at mRNA and protein levels) and enhances MMP-2 promoter activity in HEK293 cells; conditioned medium from PTTG-overexpressing cells increases cell migration, invasion, and HUVEC tubule formation; pre-treatment with MMP-2-specific antibody significantly decreases these effects. Zymography, RT-PCR, ELISA, MMP-2 promoter luciferase assay, cell migration/invasion assay, HUVEC tubule formation assay, MMP-2 antibody neutralization Molecular cancer Medium 17096843
2021 Cryo-EM structures of human separase in complex with securin and with CDK1-cyclin B1-CKS1 reveal that securin inhibits separase via pseudosubstrate motifs that block substrate binding at the catalytic site and nearby docking sites; securin contains its own pseudosubstrate motifs analogous to C. elegans and yeast securin. Cryo-electron microscopy structural determination of human separase–securin and separase–CDK1-cyclin B1-CKS1 complexes Nature High 34290405
2018 Structural review: full-length S. cerevisiae and C. elegans separase–securin structures show securin has extensive contacts with separase consistent with a chaperone function and inhibits separase by binding as a pseudo-substrate at the catalytic site. Review of crystal/cryo-EM structures of yeast and C. elegans separase–securin complexes Current opinion in structural biology Medium 29452922
2020 SGO2-MAD2 can functionally replace securin as a separase inhibitor; SGO2 uses a pseudo-substrate sequence to block the active site of separase, similar to securin; APC/C-dependent ubiquitylation and TRIP13-p31comet liberate separase from SGO2-MAD2 in vitro; acute loss of both securin and SGO2 (but not either alone) results in premature cohesin cleavage and cytotoxicity, demonstrating securin-independent separase regulation. In vitro separase liberation assay, securin-knockout cell characterization, genetic co-depletion of securin and SGO2, biochemical fractionation Nature High 32322060
2008 Dicoumarol represses PTTG1/Securin gene expression through inhibition of Hsp90; established Hsp90 inhibitors (17-AAG and novobiocin) also repress PTTG1 expression; overexpression of Hsp90 in yeast confers hypersensitivity to dicoumarol; PTTG1 repression by dicoumarol is partially attributable to inhibition of the Ras/Raf/ERK pathway. Hsp90 inhibitor treatment, Hsp90 overexpression in yeast, in vivo heat-shock luciferase recovery assay, Western blot for Hsp90 clients, pathway inhibitor analysis Molecular cancer therapeutics Medium 18347135
2011 PTTG1 attenuates drug-induced cellular senescence by suppressing p21; PTTG1-/- HCT116 cells show ~4-fold more doxorubicin/TSA-induced senescence and ~3-fold higher p21 induction; binding of Sp1, p53, and p300 to the p21 promoter is enhanced in PTTG1-/- cells after treatment; p21 knockdown abrogates the senescent effects, placing PTTG1 upstream of p21 in this pathway. PTTG1-/- cell line, SA-β-gal senescence assay, BrdU incorporation, ChIP (Sp1/p53/p300 on p21 promoter), p21 siRNA epistasis, in vivo xenograft with doxorubicin treatment PloS one High 21858218
2019 ECT2 regulates PTTG1 expression by stabilizing the E2F1 transcription factor through the deubiquitinating enzyme PSMD14; ECT2 upregulates PSMD14, which prevents E2F1 ubiquitination/degradation, allowing E2F1 to drive PTTG1 transcription and glioma cell proliferation. Co-immunoprecipitation, in vivo ubiquitination assay, Western blot, siRNA knockdown, in vivo xenograft experiments Neuro-oncology Medium 30590814
2005 Beta-catenin/TCF pathway activates PTTG transcription in esophageal squamous cell carcinoma; a TCF4-binding element (TBE) was identified in the PTTG promoter; S37A β-catenin activates PTTG promoter activity dependent on the intact TBE; TCF-4 protein binds the TBE by biotin-streptavidin pull-down; dominant-negative TCF suppresses activation. PTTG promoter luciferase assay with deletion/mutation analysis, biotin-streptavidin pull-down for TCF-4 binding, S37Aβ-catenin and dominant-negative TCF transfection International journal of cancer Medium 15514942
2014 PTTG1 promotes prostate cancer cell proliferation by inhibiting SMAD3 (a TGFβ signaling effector); PTTG1 overexpression significantly decreases SMAD3 levels; re-expression of SMAD3 rescues the PTTG1-induced proliferation; SMAD3 siRNA knockdown rescues proliferation inhibited by PTTG1 shRNA. PTTG1 transgene and shRNA in PC3 cells, Western blot for SMAD3, SMAD3 re-expression rescue, SMAD3 siRNA epistasis, in vitro and in vivo proliferation assays Tumour biology Medium 24627133
2023 PTTG1 promotes asparagine synthetase (ASNS) transcription by directly binding to its promoter, increasing asparagine (Asn) levels, which subsequently activate the mTOR pathway to facilitate HCC progression; HBx promotes ASNS and Asn metabolism by upregulating PTTG1; asparaginase treatment reverses PTTG1 overexpression-induced proliferation. PTTG1-deficient DEN-induced and HBx-induced HCC mouse models, ChIP/promoter binding assay, amino acid metabolomics, mTOR pathway Western blot, asparaginase rescue experiment Cancer research Medium 37159932
2023 PTTG1 is a bona fide β-catenin binding protein that inhibits destruction complex assembly, promoting β-catenin stabilization and nuclear localization; PTTG1 subcellular distribution is regulated by PP2A-mediated dephosphorylation at Ser165/171 (preventing nuclear translocation), reversible by PP2A inhibitor okadaic acid; PTTG1 competitively binds PP2A with GSK3β, decreasing GSK3β Ser9-phosphorylation-inactivation and indirectly stabilizing cytoplasmic β-catenin. Co-immunoprecipitation (PTTG1–β-catenin), phosphorylation mutant analysis, PP2A inhibitor treatment (okadaic acid), subcellular fractionation, Western blot, luciferase reporter for Wnt activity Oncogene Medium 37400529
2021 Nuclear localization of PTTG1 correlates with aggressive phenotype in seminoma cells and promotes invasiveness through activation of MMP-2; PTTG1 modulation (overexpression/knockdown) confirms causality; MMP-2 levels are significantly higher in seminomas where PTTG1 is nuclear. Immunofluorescence for PTTG1 nuclear vs. cytoplasmic localization, wound-healing assay, Matrigel invasion, zymography for MMP-2, RNAi and overexpression in seminoma cell lines Cancers Medium 33430117

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Isolation and characterization of a pituitary tumor-transforming gene (PTTG). Molecular endocrinology (Baltimore, Md.) 467 9092795
1999 Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. The Journal of clinical endocrinology and metabolism 333 10022450
1999 Structure, expression, and function of human pituitary tumor-transforming gene (PTTG). Molecular endocrinology (Baltimore, Md.) 282 9892021
2001 Securin degradation is mediated by fzy and fzr, and is required for complete chromatid separation but not for cytokinesis. The EMBO journal 197 11179223
2002 Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis. Nature genetics 164 12355087
1998 hpttg, a human homologue of rat pttg, is overexpressed in hematopoietic neoplasms. Evidence for a transcriptional activation function of hPTTG. Oncogene 160 9811450
2003 Securin and B-cyclin/CDK are the only essential targets of the APC. Nature cell biology 155 14634663
2014 Cdc20 and securin overexpression predict short-term breast cancer survival. British journal of cancer 132 24853182
1999 hpttg is over-expressed in pituitary adenomas and other primary epithelial neoplasias. Oncogene 130 10498901
2003 Expression of pituitary tumour transforming gene (PTTG) and fibroblast growth factor-2 (FGF-2) in human pituitary adenomas: relationships to clinical tumour behaviour. Clinical endocrinology 127 12580928
2006 Pituitary tumour transforming gene (PTTG) expression correlates with the proliferative activity and recurrence status of pituitary adenomas: a clinical and immunohistochemical study. Clinical endocrinology 118 16984249
2005 Pituitary hypoplasia in Pttg-/- mice is protective for Rb+/- pituitary tumorigenesis. Molecular endocrinology (Baltimore, Md.) 101 15919720
2001 Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase. Nucleic acids research 98 11238996
2002 Expression of PTTG (pituitary tumor transforming gene) in esophageal cancer. Japanese journal of clinical oncology 94 12324572
2019 ECT2/PSMD14/PTTG1 axis promotes the proliferation of glioma through stabilizing E2F1. Neuro-oncology 92 30590814
2012 Expression of Ki-67, PTTG1, FGFR4, and SSTR 2, 3, and 5 in nonfunctioning pituitary adenomas: a high throughput TMA, immunohistochemical study. The Journal of clinical endocrinology and metabolism 90 22419713
2000 Cell cycle regulated expression and phosphorylation of hpttg proto-oncogene product. Oncogene 90 10656688
2000 Pituitary tumor transforming gene (PTTG) regulates placental JEG-3 cell division and survival: evidence from live cell imaging. Molecular endocrinology (Baltimore, Md.) 89 10935539
2000 Cell cycle mechanisms of sister chromatid separation; roles of Cut1/separin and Cut2/securin. Genes to cells : devoted to molecular & cellular mechanisms 87 10651900
2005 Ectopic expression of PTTG1/securin promotes tumorigenesis in human embryonic kidney cells. Molecular cancer 85 15649325
2018 Long Non-coding RNA ECRAR Triggers Post-natal Myocardial Regeneration by Activating ERK1/2 Signaling. Molecular therapy : the journal of the American Society of Gene Therapy 77 30528086
2004 PTTG/securin activates expression of p53 and modulates its function. Molecular cancer 77 15242522
2021 Structural basis of human separase regulation by securin and CDK1-cyclin B1. Nature 71 34290405
2006 Regulation of angiogenesis and invasion by human Pituitary tumor transforming gene (PTTG) through increased expression and secretion of matrix metalloproteinase-2 (MMP-2). Molecular cancer 71 17096843
2005 Overexpression of human pituitary tumor transforming gene (hPTTG), is regulated by beta-catenin /TCF pathway in human esophageal squamous cell carcinoma. International journal of cancer 69 15514942
2011 PTTG induces EMT through integrin αVβ3-focal adhesion kinase signaling in lung cancer cells. Oncogene 68 22081074
2005 Pituitary tumour transforming gene (PTTG) induces genetic instability in thyroid cells. Oncogene 62 15897900
2000 Identification of the human pituitary tumor transforming gene (hPTTG) family: molecular structure, expression, and chromosomal localization. Gene 58 10806349
1999 Molecular cloning and characterization of the tumor transforming gene (TUTR1): a novel gene in human tumorigenesis. Cytogenetics and cell genetics 56 10393434
2005 Human full-length Securin is a natively unfolded protein. Protein science : a publication of the Protein Society 53 15929994
2023 PTTG1 Reprograms Asparagine Metabolism to Promote Hepatocellular Carcinoma Progression. Cancer research 52 37159932
2020 Securin-independent regulation of separase by checkpoint-induced shugoshin-MAD2. Nature 52 32322060
2000 Pituitary tumor transforming gene (PTTG) transforming and transactivation activity. The Journal of biological chemistry 51 10713046
2020 Bisphenol A promotes breast cancer cell proliferation by driving miR-381-3p-PTTG1-dependent cell cycle progression. Chemosphere 49 33352510
2008 PTTG: an important target gene for ovarian cancer therapy. Journal of ovarian research 49 19014669
2004 Expression of pituitary tumor transforming gene (PTTG) and its binding protein in human astrocytes and astrocytoma cells: function and regulation of PTTG in U87 astrocytoma cells. Endocrinology 49 15178645
2012 Expression of the PTTG1 oncogene is associated with aggressive clear cell renal cell carcinoma. Cancer research 44 22805307
2022 PCLAF promotes neuroblastoma G1/S cell cycle progression via the E2F1/PTTG1 axis. Cell death & disease 43 35210406
2007 PTTG and PBF repress the human sodium iodide symporter. Oncogene 43 17297475
2006 Suppression of lung cancer with siRNA targeting PTTG. International journal of oncology 43 16820881
2017 PTTG1 regulated by miR-146a-3p promotes bladder cancer migration, invasion, metastasis and growth. Oncotarget 42 27893422
2013 PTTG acts as a STAT3 target gene for colorectal cancer cell growth and motility. Oncogene 42 23416975
2009 PTTG overexpression promotes lymph node metastasis in human esophageal squamous cell carcinoma. Cancer research 42 19351864
2017 The clinical value and biological function of PTTG1 in colorectal cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 41 28219049
2005 Securin is overexpressed in breast cancer. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 41 15846392
2003 A potential role for PTTG/securin in the developing human fetal brain. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 38 12958169
2002 Expression of hpttg proto-oncogene in lymphoid neoplasias. Oncogene 38 12444553
2010 Expression of pituitary tumor-transforming gene 1 (PTTG1)/securin in hepatitis B virus (HBV)-associated liver diseases: evidence for an HBV X protein-mediated inhibition of PTTG1 ubiquitination and degradation. Hepatology (Baltimore, Md.) 37 20198633
2010 Pituitary senescence: the evolving role of Pttg. Molecular and cellular endocrinology 36 20153804
2019 PTTG1 is involved in TNF-α-related hepatocellular carcinoma via the induction of c-myc. Cancer medicine 34 31385458
2011 PTTG1/securin modulates microtubule nucleation and cell migration. Molecular biology of the cell 33 21937724
2003 Human pituitary tumor-transforming gene (PTTG1) motif suppresses prolactin expression. Molecular endocrinology (Baltimore, Md.) 33 12554778
2003 Human pituitary tumor transforming gene (hPTTG) inhibits human lung cancer A549 cell growth through activation of p21(WAF1/CIP1 ). Endocrine journal 33 14709851
2014 PTTG1 inhibits SMAD3 in prostate cancer cells to promote their proliferation. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 32 24627133
2005 Insulin and IGF-1 regulate the expression of the pituitary tumor transforming gene (PTTG) in breast tumor cells. FEBS letters 32 15922332
2004 An interactive gene network for securin-separase, condensin, cohesin, Dis1/Mtc1 and histones constructed by mass transformation. Genes to cells : devoted to molecular & cellular mechanisms 32 15507118
2004 PTTG's C-terminal PXXP motifs modulate critical cellular processes in vitro. Journal of molecular endocrinology 32 15591026
2019 The long non-coding RNA PTTG3P promotes growth and metastasis of cervical cancer through PTTG1. Aging 31 30853662
2015 FoxM1 transactivates PTTG1 and promotes colorectal cancer cell migration and invasion. BMC medical genomics 31 26264222
2007 Small interfering RNA against PTTG: a novel therapy for ovarian cancer. International journal of oncology 31 17549414
2010 Expression of PTTG1 and PTEN in endometrial carcinoma: correlation with tumorigenesis and progression. Medical oncology (Northwood, London, England) 29 21181309
2003 Characterization of the role of Sp1 and NF-Y in differential regulation of PTTG/securin expression in tumor cells. Gene 29 14644503
2021 CDC20 and PTTG1 are Important Biomarkers and Potential Therapeutic Targets for Metastatic Prostate Cancer. Advances in therapy 28 33881746
2009 E2F1 induces pituitary tumor transforming gene (PTTG1) expression in human pituitary tumors. Molecular endocrinology (Baltimore, Md.) 28 19837943
2019 Patronus is the elusive plant securin, preventing chromosome separation by antagonizing separase. Proceedings of the National Academy of Sciences of the United States of America 27 31324745
2019 PTTG1: a Unique Regulator of Stem/Cancer Stem Cells in the Ovary and Ovarian Cancer. Stem cell reviews and reports 27 31482269
2015 PTTG regulates the metabolic switch of ovarian cancer cells via the c-myc pathway. Oncotarget 27 26516926
2020 Estrogen-regulated PTTG1 promotes breast cancer progression by regulating cyclin kinase expression. Molecular medicine (Cambridge, Mass.) 26 32272902
2017 PTTG1-interacting protein (PTTG1IP/PBF) predicts breast cancer survival. BMC cancer 26 29078751
2006 The influence of the pituitary tumor transforming gene-1 (PTTG-1) on survival of patients with small cell lung cancer and non-small cell lung cancer. Journal of carcinogenesis 26 16426442
2023 Phosphorylated PTTG1 switches its subcellular distribution and promotes β-catenin stabilization and subsequent transcription activity. Oncogene 25 37400529
2018 MicroRNA-329-mediated PTTG1 downregulation inactivates the MAPK signaling pathway to suppress cell proliferation and tumor growth in cholangiocarcinoma. Journal of cellular biochemistry 25 30582202
2009 Induction of Dlk1 by PTTG1 inhibits adipocyte differentiation and correlates with malignant transformation. Molecular biology of the cell 25 19477929
2009 Diminished pancreatic beta-cell mass in securin-null mice is caused by beta-cell apoptosis and senescence. Endocrinology 24 19213844
2008 UV-induced degradation of securin is mediated by SKP1-CUL1-beta TrCP E3 ubiquitin ligase. Journal of cell science 24 18460583
2006 Expression and possible role of hPTTG1/securin in cutaneous malignant melanoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 24 16799481
2020 Suppression of PTTG1 inhibits cell angiogenesis, migration and invasion in glioma cells. Medical oncology (Northwood, London, England) 22 32725378
2006 Anaphase topsy-turvy: Cdk1 a securin, separase a CKI. Cell cycle (Georgetown, Tex.) 22 16340311
2020 KLF10 inhibits cell growth by regulating PTTG1 in multiple myeloma under the regulation of microRNA-106b-5p. International journal of biological sciences 21 32549754
2018 Structural biology of the separase-securin complex with crucial roles in chromosome segregation. Current opinion in structural biology 21 29452922
2011 Securin and separase modulate membrane traffic by affecting endosomal acidification. Traffic (Copenhagen, Denmark) 21 21272169
2016 PTTG1 Levels Are Predictive of Saracatinib Sensitivity in Ovarian Cancer Cell Lines. Clinical and translational science 20 27766744
2014 Prostate cancer cell response to paclitaxel is affected by abnormally expressed securin PTTG1. Molecular cancer therapeutics 20 25122070
2013 Expression of pituitary tumor transforming gene (PTTG) in human pituitary macroadenomas. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 20 23404407
2010 Immunohistochemical expression of pituitary tumor transforming gene (PTTG) in pituitary adenomas: a correlative study of tumor subtypes. International journal of surgical pathology 20 20106827
2017 Targeting the PTTG1 oncogene impairs proliferation and invasiveness of melanoma cells sensitive or with acquired resistance to the BRAF inhibitor dabrafenib. Oncotarget 19 29371923
2015 Roles of miR-186 and PTTG1 in colorectal neuroendocrine tumors. International journal of clinical and experimental medicine 19 26885189
2011 PTTG1 attenuates drug-induced cellular senescence. PloS one 19 21858218
2007 PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes. Molecular cancer 19 17222350
2016 Inhibition of PTTG1 expression by microRNA suppresses proliferation and induces apoptosis of malignant glioma cells. Oncology letters 18 27900021
2013 Low cdc27 and high securin expression predict short survival for breast cancer patients. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 18 23755904
2012 A single mutation in Securin induces chromosomal instability and enhances cell invasion. European journal of cancer (Oxford, England : 1990) 18 22819078
2021 Nuclear Localization of PTTG1 Promotes Migration and Invasion of Seminoma Tumor through Activation of MMP-2. Cancers 17 33430117
2014 Pttg1 inhibits TGFβ signaling in breast cancer cells to promote their growth. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 17 25227666
2011 Glycogen synthase kinase-3beta (GSK3beta) negatively regulates PTTG1/human securin protein stability, and GSK3beta inactivation correlates with securin accumulation in breast tumors. The Journal of biological chemistry 17 21757741
2009 Histone acetyltransferase p300 regulates the expression of human pituitary tumor transforming gene (hPTTG). Journal of genetics and genomics = Yi chuan xue bao 17 19539243
2008 Dicoumarol down-regulates human PTTG1/Securin mRNA expression through inhibition of Hsp90. Molecular cancer therapeutics 17 18347135
2021 The Clinical Significance and Potential Molecular Mechanism of PTTG1 in Esophageal Squamous Cell Carcinoma. Frontiers in genetics 16 33552118
2014 Relationship of PTTG expression with tumor invasiveness and microvessel density of pituitary adenomas: a meta-analysis. Genetic testing and molecular biomarkers 16 24611443
2003 PTTG and cancer. Histology and histopathology 15 12507303

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