927 results match your criteria securin

The lncRNA PTTG3P promotes the progression of CRPC via upregulating PTTG1.

Bull Cancer 2021 Apr 18;108(4):359-368. Epub 2021 Mar 18.

Chongqing medical university, The third affiliated hospital (General Hospital), Department of urology, 401120 Chongqing, China. Electronic address:

Background: Overexpression of certain long non-coding RNAs (lncRNAs) promotes the progression of castration-resistant prostate cancer (CRPC). The significance and potential role of the lncRNA designated pituitary tumour-transforming 3, pseudogene (PTTG3P) in CRPC is unknown.

Methods: We detected PTTG3P expression by qPCR. Read More

View Article and Full-Text PDF

Deprotection of centromeric cohesin at meiosis II requires APC/C activity but not kinetochore tension.

EMBO J 2021 Apr 1;40(7):e106812. Epub 2021 Mar 1.

Laboratory of Chromosome Biology, Max Planck Institute of Biochemistry, Martinsried, Germany.

Genome haploidization involves sequential loss of cohesin from chromosome arms and centromeres during two meiotic divisions. At centromeres, cohesin's Rec8 subunit is protected from separase cleavage at meiosis I and then deprotected to allow its cleavage at meiosis II. Protection of centromeric cohesin by shugoshin-PP2A seems evolutionarily conserved. Read More

View Article and Full-Text PDF

[MiR-300 inhibits invasion and metastasis of osteosarcoma cell MG63 by negatively regulating PTTG1].

Nan Fang Yi Ke Da Xue Xue Bao 2021 Feb;41(2):285-291

First Department of Joint Surgery, Affiliated Hospital of Weifang Medical College, Weifang Medical University, Weifang 26105, China.

Objective: To investigate the effects of miR-300 and PTTG1 on osteosarcoma invasion and metastasis and explore the molecular mechanism of osteosarcoma invasion and metastasis.

Objective: Western blot was used to detect the expression of PTTG1 in human osteoblasts hFOB1.19 and osteosarcoma cell MG63 and to detect the transfection efficiency of cells transfected with PTTG1-knockdown plasmid; Transwell invasion assay and CCK8 assay detected the effects of knockdown of PTTG1 and overexpression of miR-300 on the invasion and proliferation of osteosarcoma cell MG63. Read More

View Article and Full-Text PDF
February 2021

Alteration of Pituitary Tumor Transforming Gene 1 by MicroRNA-186 and 655 Regulates Invasion Ability of Human Oral Squamous Cell Carcinoma.

Int J Mol Sci 2021 Jan 20;22(3). Epub 2021 Jan 20.

Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea.

Background: Pituitary tumor-transforming gene 1 (PTTG1) was recently shown to be involved in the progression as well as the metastasis of cancers. However, their expression and function in the invasion of oral squamous cell carcinoma (SCC) remain unclear.

Methods: The expressions of PTTG1 and PTTG1-targeted miRNA in oral SCC cell lines and their invasion capability depended on PTTG1 expression were analyzed by quantitative RT-PCR, Western blots, the transwell insert system and Zymography. Read More

View Article and Full-Text PDF
January 2021

Mechanisms Applied by Protein Inhibitors to Inhibit Cysteine Proteases.

Int J Mol Sci 2021 Jan 20;22(3). Epub 2021 Jan 20.

Department of Biochemistry and Molecular and Structural Biology, Jozef Stefan Institute, Jamova Cesta 39, 1000 Ljubljana, Slovenia.

Protein inhibitors of proteases are an important tool of nature to regulate and control proteolysis in living organisms under physiological and pathological conditions. In this review, we analyzed the mechanisms of inhibition of cysteine proteases on the basis of structural information and compiled kinetic data. The gathered structural data indicate that the protein fold is not a major obstacle for the evolution of a protease inhibitor. Read More

View Article and Full-Text PDF
January 2021

Fisetin: An anticancer perspective.

Food Sci Nutr 2021 Jan 25;9(1):3-16. Epub 2020 Nov 25.

The University of Gambia Sere Kunda Gambia.

Despite the provision of safe and cost-effective chemopreventive cancer approaches, still there are requirements to enhance their efficiency. The use of dietary agents as phytochemicals plays an imperative role against different human cancer cell lines. Among these novel dietary agents, fisetin (3,3',4',7-tetrahydroxyflavone) is present in different fruits and vegetables such as apple, persimmon, grape, strawberry, cucumber, and onion. Read More

View Article and Full-Text PDF
January 2021

Structure and Function of the Separase-Securin Complex.

Subcell Biochem 2021 ;96:217-232

Department of Biological Sciences, Columbia University, New York, NY, 10027, USA.

Separase is a large cysteine protease in eukaryotes and has crucial roles in many cellular processes, especially chromosome segregation during mitosis and meiosis, apoptosis, DNA damage repair, centrosome disengagement and duplication, spindle stabilization and elongation. It dissolves the cohesion between sister chromatids by cleaving one of the subunits of the cohesin ring for chromosome segregation. The activity of separase is tightly controlled at many levels, through direct binding of inhibitory proteins as well as posttranslational modification. Read More

View Article and Full-Text PDF
February 2021

[Expression of pituitary tumor-transforming gene-1 and its pathogenic role in systemic sclerosis].

Nan Fang Yi Ke Da Xue Xue Bao 2020 Nov;40(11):1564-1570

Department of Dermatology, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China.

Objective: To investigate the expression of tumor-transforming gene-1 (PTTG1) in systemic sclerosis (SSc) and its role in fibrosis.

Methods: Skin biopsy samples were collected from 21 patients with SSc and 22 patients with healthy skin for detecting the mRNA and protein expressions of PTTG1 using real-time PCR (RT-PCR) and immunohistochemistry, respectively. In cultured primary human dermal fibroblasts, PTTG1 expression was knocked down via RNA interference (siRNA), and the mRNA expression levels of PTTG1 and the fibrosis-related genes -SMA, COL1A1, COL1A2, and COL3A1 were detected using RT-PCR; the proliferation of the cells was assessed using a real-time cell proliferation detection system. Read More

View Article and Full-Text PDF
November 2020

Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit.

Elife 2020 09 1;9. Epub 2020 Sep 1.

Department of Biochemistry, University of Oxford, Oxford, United Kingdom.

APC/C-mediated proteolysis of cyclin B and securin promotes anaphase entry, inactivating CDK1 and permitting chromosome segregation, respectively. Reduction of CDK1 activity relieves inhibition of the CDK1-counteracting phosphatases PP1 and PP2A-B55, allowing wide-spread dephosphorylation of substrates. Meanwhile, continued APC/C activity promotes proteolysis of other mitotic regulators. Read More

View Article and Full-Text PDF
September 2020

PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20.

Mol Biol Cell 2020 10 5;31(21):2315-2330. Epub 2020 Aug 5.

Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.

Ubiquitin-dependent proteolysis of cyclin B and securin initiates sister chromatid segregation and anaphase. The anaphase-promoting complex/cyclosome and its coactivator CDC20 (APC/C) form the main ubiquitin E3 ligase for these two proteins. APC/C is regulated by CDK1-cyclin B and counteracting PP1 and PP2A family phosphatases through modulation of both activating and inhibitory phosphorylation. Read More

View Article and Full-Text PDF
October 2020

PP2A dephosphorylates Pds1 and inhibits spindle elongation in .

J Cell Sci 2020 07 29;133(14). Epub 2020 Jul 29.

Biology Department, Brooklyn College, The City University of New York, Brooklyn, NY 11238, USA

PP2A (the form of protein phosphatase 2A containing Cdc55) regulates cell cycle progression by reversing cyclin-dependent kinase (CDK)- and polo-like kinase (Cdc5)-dependent phosphorylation events. In , Cdk1 phosphorylates securin (Pds1), which facilitates Pds1 binding and inhibits separase (Esp1). During anaphase, Esp1 cleaves the cohesin subunit Scc1 and promotes spindle elongation. Read More

View Article and Full-Text PDF

A prognostic model based on cell-cycle control predicts outcome of breast cancer patients.

BMC Cancer 2020 Jun 16;20(1):558. Epub 2020 Jun 16.

Institute of Biomedicine, University of Turku, Turku, Finland.

Background: A prognostic model combining biomarkers of metaphase-anaphase transition of the cell cycle was developed for invasive breast cancer. The prognostic value and clinical applicability of the model was evaluated in comparison with the routine prognosticators of invasive breast carcinoma.

Methods: The study comprised 1135 breast cancer patients with complete clinical data and up to 22-year follow-up. Read More

View Article and Full-Text PDF

[Pituitary tumor transforming gene 1 (PTTG1) is highly expressed and associated with poor prognosis in patients with hepatocellular carcinoma].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2020 Apr;36(4):337-343

Department of Human Anatomy, Key Laboratory of Transplantation of Anhui Province, Bengbu Medical College, Bengbu 233030, China. *Corresponding author, E-mail:

Objective To analyze the expression of pituitary tumor transforming gene 1 (PTTG1) in hepatocellular carcinoma (HCC) and its clinical prognostic implication. Methods Firstly, the Tumorsurvival and HCCDB databases were used to analyze the expression of PTTG1 gene and its co-expressed genes in HCC tissues. Secondly, cBioPortal, MetaScape, Kaplan-Meier Plotter databases were used to analyze the mutations, GO functions and KEGG of the co-expressed genes of PTTG1 in HCC, and to analyze the effects of co-expressed genes on the overall survival (OS) and prognosis of HCC patients. Read More

View Article and Full-Text PDF

Cell division cycle 23 is required for mouse oocyte meiotic maturation.

FASEB J 2020 07 25;34(7):8990-9002. Epub 2020 May 25.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Precise regulation of chromosome segregation during oocyte meiosis is of vital importance to mammalian reproduction. Anaphase promoting complex/cyclosome (APC/C) is reported to play an important role in metaphase-to-anaphase transition. Here we report that cell division cycle 23 (Cdc23, also known as APC8) plays a critical role in regulating the oocyte chromosome separation. Read More

View Article and Full-Text PDF

Dun1, a Chk2-related kinase, is the central regulator of securin-separase dynamics during DNA damage signaling.

Nucleic Acids Res 2020 06;48(11):6092-6107

Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Proteos, 61 Biopolis Drive, Singapore.

The DNA damage checkpoint halts cell cycle progression in G2 in response to genotoxic insults. Central to the execution of cell cycle arrest is the checkpoint-induced stabilization of securin-separase complex (yeast Pds1-Esp1). The checkpoint kinases Chk1 and Chk2 (yeast Chk1 and Rad53) are thought to critically contribute to the stability of securin-separase complex by phosphorylation of securin, rendering it resistant to proteolytic destruction by the anaphase promoting complex (APC). Read More

View Article and Full-Text PDF

Securin-independent regulation of separase by checkpoint-induced shugoshin-MAD2.

Nature 2020 04 8;580(7804):536-541. Epub 2020 Apr 8.

Chair of Genetics, University of Bayreuth, Bayreuth, Germany.

Separation of eukaryotic sister chromatids during the cell cycle is timed by the spindle assembly checkpoint (SAC) and ultimately triggered when separase cleaves cohesion-mediating cohesin. Silencing of the SAC during metaphase activates the ubiquitin ligase APC/C (anaphase-promoting complex, also known as the cyclosome) and results in the proteasomal destruction of the separase inhibitor securin. In the absence of securin, mammalian chromosomes still segregate on schedule, but it is unclear how separase is regulated under these conditions. Read More

View Article and Full-Text PDF

A unique binding mode of Nek2A to the APC/C allows its ubiquitination during prometaphase.

EMBO Rep 2020 06 19;21(6):e49831. Epub 2020 Apr 19.

MRC Laboratory of Molecular Biology, Cambridge, UK.

The anaphase-promoting complex (APC/C) is the key E3 ubiquitin ligase which directs mitotic progression and exit by catalysing the sequential ubiquitination of specific substrates. The activity of the APC/C in mitosis is restrained by the spindle assembly checkpoint (SAC), which coordinates chromosome segregation with the assembly of the mitotic spindle. The SAC effector is the mitotic checkpoint complex (MCC), which binds and inhibits the APC/C. Read More

View Article and Full-Text PDF

Nocodazole-Induced Expression and Phosphorylation of Anillin and Other Mitotic Proteins Are Decreased in DNA-Dependent Protein Kinase Catalytic Subunit-Deficient Cells and Rescued by Inhibition of the Anaphase-Promoting Complex/Cyclosome with proTAME but Not Apcin.

Mol Cell Biol 2020 06 15;40(13). Epub 2020 Jun 15.

Department of Biochemistry and Molecular Biology and Robson DNA Science Centre, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has well-established roles in DNA double-strand break repair, and recently, nonrepair functions have also been reported. To better understand its cellular functions, we deleted DNA-PKcs from HeLa and A549 cells using CRISPR/Cas9. The resulting cells were radiation sensitive, had reduced expression of ataxia-telangiectasia mutated (ATM), and exhibited multiple mitotic defects. Read More

View Article and Full-Text PDF

aarF domain containing kinase 5 gene promotes invasion and migration of lung cancer cells through ADCK5-SOX9-PTTG1 pathway.

Exp Cell Res 2020 07 8;392(1):112002. Epub 2020 Apr 8.

Department of Thoracic Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China. Electronic address:

AarF domain containing kinase 5 (ADCK5) is a member of an atypical kinase family and overexpressed in many carcinomas including lung cancer, while the function of this protein has not been elucidated. Here we investigated the mechanism of ADCK5 involved in regulating invasion and migration of lung cancer cells, and showed that ADCK5 might regulate the expression of tumor oncogene human pituitary tumor transforming gene-1 (PTTG1) by phosphorylating transcription factor SOX9, therefore enhancing the migration and invasion capabilities of lung cancer cells. Mutagenesis of potential serine phosphorylation sites on SOX9 indicated that serine 181 might be required to maintain transcription activation of SOX9 as well as increase PTTG1 levels. Read More

View Article and Full-Text PDF

[Down-regulated PTTG1 expression promotes the senescence of human prostate cancer LNCaP-AI].

Zhonghua Nan Ke Xue 2019 Mar;25(3):216-222

Department of Urology, Xuzhou First People's Hospital, Xuzhou, Jiangsu 221004, China.

Objective: To investigate the effect of the down-regulated expression of pituitary tumor-transforming gene 1 (PTTG1) on the senescence of human castration-resistant prostate cancer LNCaP-AI cells.

Methods: Human castration-resistant prostate cancer LNCaP-AI cells were induced in vitro and transfected with siRNA targeting PTTG1 (the siRNA-PTTG1 group), the reagent lip3000 only (the mock group) or siRNA negative control vector (the NC group). All the cells were cultured in fetal bovine serum (FBS) or charcoal-stripped bovine serum (CSS) and counted with the cell counting chamber. Read More

View Article and Full-Text PDF

[The Influence of the Minor Short Isoform of Securin (PTTG1) on Transcription is Significantly Different from the Impact of the Full Isoform].

Mol Biol (Mosk) 2020 Jan-Feb;54(1):51-59

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.

PTTG1 (vertebrate securin) is a separation inhibitor and regulates DNA repair and transcription. The protein is predominantly expressed in the second half of the S phase and at the G2 stage. With the onset of anaphase, securin is ubiquitinated by the APC/C complex and degraded rapidly. Read More

View Article and Full-Text PDF

Analysis and Identification of Tumorigenic Targets of MicroRNA in Cancer Cells by Photoreactive Chemical Probes.

Int J Mol Sci 2020 Feb 24;21(4). Epub 2020 Feb 24.

School of Chemistry & Chemical Engineering, Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, Inner Mongolia University, 235 West College Road, Hohhot, Inner Mongolia 010020, China.

Photoactive RNA probes have unique advantages in the identification of microRNA (miR) targets due to their ability for efficient conjugation to the target sequences by covalent crosslinking, providing stable miR-mRNA complexes for further analysis. Here, we report a highly efficient and straightforward method for miR target identification that is based on photo-reactive chemical probes and RNA-seq technology (denotes PCP-Seq). UV reactive probes were prepared by incorporating psoralen in the specific position of the seed sequence of miR. Read More

View Article and Full-Text PDF
February 2020

Of mice, genes and aging.

James DeGregori

Haematologica 2020 31;105(2):246-248. Epub 2020 Jan 31.

Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

View Article and Full-Text PDF

Prognostic value of mitotic checkpoint protein BUB3, cyclin B1, and pituitary tumor-transforming 1 expression in prostate cancer.

Mod Pathol 2020 05 4;33(5):905-915. Epub 2019 Dec 4.

Institute for Cancer Genetics and Informatics, Oslo University Hospital, NO-0424, Oslo, Norway.

The mitotic checkpoint protein BUB3, cyclin B1 (CCNB1) and pituitary tumor-transforming 1 (PTTG1) regulates cell division, and are sparsely studied in prostate cancer. Deregulation of these genes can lead to genomic instability, a characteristic of more aggressive tumors. We aimed to determine the expression levels of BUB3, CCNB1, and PTTG1 as potential prognostic markers of recurrence after radical prostatectomy. Read More

View Article and Full-Text PDF

Methanolic extract of Potentilla fulgens root and its ethyl-acetate fraction delays the process of carcinogenesis in mice.

Sci Rep 2019 11 18;9(1):16985. Epub 2019 Nov 18.

Molecular Genetics Laboratory, Department of Biotechnology & Bioinformatics, North-Eastern Hill University, Shillong, Meghalaya, 793022, India.

People of north-eastern states of India consume raw areca-nut (RAN) and lime which could lead to oral, esophageal and gastric cancers. However, the incidence of these cancers are significantly lesser in those who consume pieces of Potentilla fulgens root along with RAN. Since evaluation of anticancer role, if any, of P. Read More

View Article and Full-Text PDF
November 2019

Cohesin cleavage by separase is enhanced by a substrate motif distinct from the cleavage site.

Nat Commun 2019 11 15;10(1):5189. Epub 2019 Nov 15.

Department of Physiology, University of California, San Francisco, CA, 94143, USA.

Chromosome segregation begins when the cysteine protease, separase, cleaves the Scc1 subunit of cohesin at the metaphase-to-anaphase transition. Separase is inhibited prior to metaphase by the tightly bound securin protein, which contains a pseudosubstrate motif that blocks the separase active site. To investigate separase substrate specificity and regulation, here we develop a system for producing recombinant, securin-free human separase. Read More

View Article and Full-Text PDF
November 2019

The cyclin B2/CDK1 complex inhibits separase activity in mouse oocyte meiosis I.

Development 2019 12 2;146(23). Epub 2019 Dec 2.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China

Chromosome segregation is driven by separase, activity of which is inhibited by binding to securin and cyclin B1/CDK1. In meiosis, premature separase activity will induce aneuploidy or abolish chromosome segregation owing to the untimely destruction of cohesin. Recently, we have proved that cyclin B2 can compensate for cyclin B1 in CDK1 activation for the oocyte meiosis G2/M transition. Read More

View Article and Full-Text PDF
December 2019

Ubiquitin-specific protease 8 inhibitor suppresses adrenocorticotropic hormone production and corticotroph tumor cell proliferation.

Endocr J 2020 Feb 30;67(2):177-184. Epub 2019 Oct 30.

Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan.

Cushing's disease is primarily caused by autonomic hypersecretion of adrenocorticotropic hormone (ACTH) from a pituitary adenoma. In Cushing's disease, mutations in the ubiquitin-specific protease 8 (USP8) have been detected. These mutations are associated with hyperactivation of USP8 that prevent epidermal growth factor receptor (EGFR) degradation. Read More

View Article and Full-Text PDF
February 2020

Validation of the OncoMasTR Risk Score in Estrogen Receptor-Positive/HER2-Negative Patients: A TransATAC study.

Clin Cancer Res 2020 02 22;26(3):623-631. Epub 2019 Oct 22.

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.

Purpose: To test the validity of OncoMasTR Molecular Score (OMm), OMclin1, and OncoMasTR Risk Score (OMclin2) prognostic scores for prediction of distant recurrence (DR) in estrogen receptor (ER)-positive/HER2-negative breast cancer treated with 5 years' endocrine therapy only and compare their performance with the Oncotype DX Recurrence Score (RS).

Experimental Design: OMm incorporates three master transcription regulator genes. OMclin1 combines OMm, tumor size, grade, and nodal status; OMclin2 incorporates OMm, tumor size, and nodal status. Read More

View Article and Full-Text PDF
February 2020

Degradation of Ccnb3 is essential for maintenance of MII arrest in oocyte.

Biochem Biophys Res Commun 2020 01 19;521(1):265-269. Epub 2019 Oct 19.

Fertility Preservation Lab, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China. Electronic address:

Before fertilization, ovulated mammalian oocytes are arrested at the metaphase of second meiosis (MII), which is maintained by the so-called cytostatic factor (CSF). It is well known that the continuous synthesis and accumulation of cyclin B is critical for maintaining the CSF-mediated MII arrest. Recent studies by us and others have shown that Ccnb3 is required for the metaphase-to-anaphase transition during the first meiosis of mouse oocytes, but whether Ccnb3 plays a role in MII arrest and exit remains unknown. Read More

View Article and Full-Text PDF
January 2020