basic FUNCTION
| mitotic checkpoint protein which inhibits sister chromatid separation during mitosis |
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maintenance of euploidy and chromosomal stability |
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involved in tumor angiogenesis and mitogenesis |
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playing a potential role in modulating cell proliferation and FGF2 expression during neurogenesis |
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involved in proliferation, and aggressiveness of prolactin pituitary tumors |
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proto-oncogene implicated in the pathogenesis of thyroid tumours |
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involved in multiple cellular pathways including cell transformation, apoptosis, DNA repair, genomic instability, mitotic control and angiogenesis induction |
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new functional role of PTTG1 and separase in the modulation of membrane traffic and protein secretion that implicates regulation of V-ATPase assembly and function |
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is a tumor cell marker to predict anti-neoplastic treatment outcomes |
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role of PTTG1 in microtubule nucleation and cell polarization, two processes directly involved in cell migration |
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participate in maintaining chromosomal integrity during the cell cycle through regulation of metaphase-anaphase transition, DNA damage repair, and apoptosis |
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enhances proliferation and suppresses early differentiation of keratinocytes |
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regulator of sister chromatid separation and transition from metaphase to anaphase |
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enhances the migratory and invasive properties of breast cancer cells by inducing epithelial to mesenchymal transition |
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oncogene implicated in malignant progression of both endocrine and nonendocrine malignancies |
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having a central role in thyroid autocrine signaling mechanisms via growth factors, with profound implications for promotion of transformed cell growth |
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securin is an inhibitor of separase (a protease required for the separation of sister chromatids in mitosis and meiosis) |
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implicated in the regulation of homotypic spacing between specific types of retinal neurons |
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promotes the progression of ovarian cancer cells, and its loss resists tumor development, in part, by regulating cellular metabolic reprogramming that supports cell growth and proliferation via MYC pathway |
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PTTG1 can control trophoblast invasion ability via regulation of MMP expression through integrin/Rho-family signaling |
CELLULAR PROCESS
| cell cycle,division,meiosis
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| cell cycle, checkpoint
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nucleotide, genomic integrity
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a component
| forms a complex with proteins involved in microtubule nucleation |
protein
| inhibiting the anaphase specific autocleavage of separin (ESPL1) |
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cohesins CDC20, APC (for sister chromatin cohesion) |
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specifically interacting with KUP70 in the Ku heterodimer association prevented by DNA double-strand breaks |
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PTTG1 and its binding factor PTTG1IP repress expression of sodium iodide symporter (NIS) messenger RNA (mRNA), and inhibit iodide uptake |
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FGF2 |
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competes with CDC20 for binding to securin, and thereby the interaction between BUB1B and PTTG1 is greatly increased by the depletion of CDC20 |
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interaction between TERT and PTTG1 by association of XRCC6 might be important for the enhancement of the limited self-renewal activity of MSCs and for understanding the regulatory mechanisms of self-renewal |
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RASGRF1 is an important upstream component of signal transduction pathways regulating PTTG1 expression and controlling beta cell development and physiological responses |
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PTTG1 is likely a novel downstream target gene of androgen receptor and take part in prostate cancer proliferation and metastasis |
repressed by
| HDAC3 (decreased PTTG1 promoter activity) |
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| KLF6 |
Phosphorylated by
| GSK3B (GSK3B phosphorylates securin to promote its proteolysis via the SKP1-CUL1-F-box protein (SCF) complex E3 ubiquitin ligase) |
Other
| regulated by EP300 (overexpression of histone acetyltransferase (HAT) p300 upregulated PTTG1 at the levels of promoter activity, mRNA and protein expression) |
Other morbid association(s)
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Type | Gene Modification | Chromosome rearrangement | Protein expression | Protein Function
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tumoral
|  
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| --low
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in T-cell leukemia | tumoral
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| --over
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in Jurkat cells in hematopoietic malignancies, pituitary, adrenal, kidney, liver, ovarian, testicular, thyroid, breast cancer | tumoral
|  
|  
| --over
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is higher in aggressive brain tumors including medulloblastomas, glioblastoma multiforme IV, and astrocytoma III, whereas in more benign tumors, PTTG immunoexpression is lower | tumoral
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| amplification
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|  
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in clear cell renal cell carcinoma | tumoral
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| --over
|  
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in breast cancer patients, compared with normal tissues | constitutional
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| --over
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in normal human fibroblasts caused chromosome instability, which subsequently induced TP53-dependent senescence through activation of DNA-damage response pathway | tumoral
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| --over
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PTTG1 and TAGLN2 are highly expressed in human pancreatic cancer | tumoral
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| --over
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in metastasis prostate cancer tissue | tumoral
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| --low
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in breast tumors, PTTG1 protein levels were down-regulated and the reduction was significantly correlated with the tumor grade | |
Variant & Polymorphism
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Candidate gene
Marker
| potential new prognosticator for treatment decisions concerning breast cancer patients | |
CDC27 and PTTG1 appear promising biomarkers for applications in predicting disease progression, prognostication of breast cancer | |
is a promising target for gastric cancer diagnosis and therapy | Therapy target
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System | Type | Disorder | Pubmed |
cancer | urinary | | |
may offer a novel therapeutic target of pathologic significance in aggressive clear cell renal cell carcinoma | cancer | reproductive | breast | |
may represent a new therapeutic target for malignant breast cancer | cancer | digestive | pancreas | |
may represent a potential therapeutic target for the treatment of pancreatic cancer | cancer | | | |
MTOR-PTTG1 signaling axis may be targeted for the treatment of tumors with MTOR hyperactivation |
| | |
| mice lacking Pttg1 developed spontaneous mammary tumors |