• p21CIP1 is a potent, tight-binding inhibitor of Cdks and can inhibit the phosphorylation of Rb by cyclin A-Cdk2, cyclin E-Cdk2, cyclin D1-Cdk4, and cyclin D2-Cdk4 complexes. (nih.gov)
  • Human cells contain many different cyclins binding to different CDKs. (wikipedia.org)
  • CDKs and cyclins appear and activate at specific cell cycle phases. (wikipedia.org)
  • Further research has demonstrates that Cdks, cyclins and CKIs play essential roles in processes such as transcription, epigenetic regulation, metabolism, stem cell self-renewal, neuronal functions and spermatogenesis. (wikipedia.org)
  • They are expressed in higher numbers in G1 cells to make sure that no S or M CDKs are in the cell. (wikipedia.org)
  • CDKs are activated by cyclins, which are expressed in distinct phases during the cell cycle. (onkoview.com)
  • Importantly, CDKs are inhibited by specific cyclin dependent kinase inhibitors. (onkoview.com)
  • If a cell becomes cancerous, though, the work of CDKs can cause the proliferation of the cancer, allowing cancerous cells to continue to divide, multiply, and spread throughout the body . (forbes.com)
  • This resistance is not unique to CDKs and CDK inhibitors: for example, a new flu shot is available every year because the flu virus may have developed immunity to prior year's shot, mitigating its usefulness. (forbes.com)
  • Further studies on its effect on cyclins and cyclin-dependent kinases (CDKs) [not measured in our study] may shed light on new treatment options for COVID-19. (biomedcentral.com)
  • Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases that act as key regulatory elements in cell cycle progression. (proteopedia.org)
  • The profiling of compound 51 against a panel of 339 kinases revealed high selectivity for CDKs, with preference for CDK2 and CDK5 over CDK9, CDK1, CDK4, and CDK6. (proteopedia.org)
  • p21, also known as senescent cell-derived inhibitor 1 (Sdi1), wild-type p53-activated fragment 1 (Waf1), Cdk-interacting protein 1 (Cip1), and p53-regulated inhibitor of Cdks (Pic1) inhibits cyclin D-cdk4, cyclin E-cdk3, cyclin A-cdk2, and cyclin A-cdk1. (bdbiosciences.com)
  • The homeodomain transcription factor MEOX2 is an important regulator of vascular cell proliferation and is a direct transcriptional activator of both p21(CIP1/WAF1) and p16(INK4a). (nih.gov)
  • Cancer develops when the balance between cell proliferation and cell death is disrupted, and the ensuing aberrant proliferation leads to tumor growth. (aacrjournals.org)
  • As a proliferation inhibitor, p21 is poised to play an important role in preventing tumor development. (aacrjournals.org)
  • However, a number of recent studies have pointed out that in addition to being an inhibitor of cell proliferation, p21 acts as an inhibitor of apoptosis in a number of systems, and this may counteract its tumor-suppressive functions as a growth inhibitor. (aacrjournals.org)
  • Active cyclin/Cdk complexes phosphorylate and inactivate members of the retinoblastoma protein (Rb) family that are negative regulators of G 1 and S-phase progression, leading to induction of E2F-regulated gene expression and cell proliferation. (aacrjournals.org)
  • In glioma ( 28 ) and in vascular smooth muscle cells ( 29 ), p21 facilitates active cyclin-Cdk complex formation and induces cell proliferation. (aacrjournals.org)
  • Without p16(INK4A) to regulate cell growth and division (proliferation), cells can continue to grow and divide without control, which can lead to tumor formation. (medlineplus.gov)
  • In addition, estrogen receptor alpha (ESR1)-mediated stimulation of proliferation of the epithelial cells contributes to conversion of DNA damage into mutations (i.e., tumor initiation) as well as tumor promotion and progression (Yager 2015 ). (springer.com)
  • ESR1-mediated proliferation involves complex intercellular signaling between epithelial and stromal cells (Lanigan et al. (springer.com)
  • 2. Cellular mechanism through which parathyroid hormone-related protein induces proliferation in arterial smooth muscle cells: definition of an arterial smooth muscle PTHrP/p27kip1 pathway. (nih.gov)
  • 6. Adenovirus-mediated overexpression of a cyclin-dependent kinase inhibitor, p57Kip2, suppressed vascular smooth muscle cell proliferation. (nih.gov)
  • 11. RNA interference targeting ORC1 gene suppresses the proliferation of vascular smooth muscle cells in rats. (nih.gov)
  • 14. Overexpression of delta Np63 in a human nasopharyngeal carcinoma cell line downregulates CKIs and enhances cell proliferation. (nih.gov)
  • 17. Antiproliferative action of cudraflavone B, isolated from Cudrania tricuspidata, through the downregulation of pRb phosphorylation in aortic smooth muscle cell proliferation signaling. (nih.gov)
  • The BDO2-treated LU cells were evaluated for cell cycle progression, nuclear localization of arrest mediators, mitotic index, and cellular proliferation. (nih.gov)
  • The BDO2-treated cells demonstrated a substantial inhibition of cell proliferation when treated with 100 microM BDO2 for 1 hr. (nih.gov)
  • Flow cytometric analysis revealed that the lack of proliferation in BDO2-treated LU cells was related to G1 arrest in about half of the cells and a delayed progression through S and G2 arrest in nearly all of the remaining cells. (nih.gov)
  • Inhibits the proliferation of a large range of cells, mainly through arresting the cells in the G2/M phase of the cell cycle. (agscientific.com)
  • Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). (proteopedia.org)
  • Compound 51 inhibited the proliferation of 13 out of 15 cancer cell lines with IC50 values between 0.27 and 6.9 muM, which correlated with the complete suppression of retinoblastoma phosphorylation and the onset of apoptosis. (proteopedia.org)
  • The cyclin-dependent kinase (Cdk) inhibitor p21Cip1 (p21) plays a crucial role in restraining cellular proliferation and maintaining cellular quiescence. (blogspot.com)
  • In vitro, proliferation is higher in neuronal progenitor cells derived from p21-/- mice compared to cells derived from wild-type mice. (blogspot.com)
  • Proliferation is increased in neuronal progenitor cells after suppression of p21 using lentivirus expressing short hairpin RNA against p21. (blogspot.com)
  • Specificity protein 1 (Sp1) has already been examined and plays important physiological roles such as cell cycle regulation, cell proliferation, and cell apoptosis ( 25 ). (spandidos-publications.com)
  • It inhibits endothelial cell proliferation and migration [5]. (who.int)
  • It moves into the cytoplasm and eventually activates a specific cyclin-dependent kinase (CDK). (wikipedia.org)
  • A cyclin-dependent kinase inhibitor protein (also known as CKIs, CDIs, or CDKIs) is a protein which inhibits the enzyme cyclin-dependent kinase (CDK) and Cyclin activity by stopping the cell cycle if there are unfavorable conditions, therefore, acting as tumor suppressors. (wikipedia.org)
  • 2006) Bruno inhibits the expression of mitotic cyclins during the prophase I meiotic arrest of Drosophila oocytes. (nih.gov)
  • Although cyclin-dependent kinase 5 (Cdk5) inhibits the formation of junctions containing N-cadherin, the effect of Cdk5 on junctions containing E-cadherin is less clear. (molvis.org)
  • Thus, Cdk5 activity promotes stability of E-cadherin-based cell-cell junctions and inhibits the E-cadherin-to-N-cadherin switch typical of epithelial-mesenchymal transitions. (molvis.org)
  • Many studies have demonstrated that Manu A inhibits cell viability and induces cell apoptosis in many cancers, such as prostate cancer, multiple myeloma, anaplastic thyroid cancer and colon cancer ( 14 - 17 ). (spandidos-publications.com)
  • Cotransfection experiments indicate that CIP1 and SV40 T antigen function in a mutually antagonistic manner to control cell cycle progression. (nih.gov)
  • Cell cycle progression is stopped by Cyclin-dependent kinase inhibitor protein at the G1 phase. (wikipedia.org)
  • 3 complexes regulates progression through the cell cycle (reviewed in Refs. (aacrjournals.org)
  • CKIs bind and inhibit the activity of cyclin/Cdk complexes and negatively regulate cell cycle progression (reviewed in Refs. (aacrjournals.org)
  • However, binding of p16(INK4A) blocks CDK4's or CDK6's ability to stimulate cell cycle progression. (medlineplus.gov)
  • p57(kip2), is involved in the cell cycle progression of vascular smooth muscle cells. (nih.gov)
  • 16. Double blockade of cell cycle progression by coptisine in vascular smooth muscle cells. (nih.gov)
  • This study examined the effect of the most active BD metabolite, butadiene diepoxide (BDO2), on cell cycle entry and progression in human lung fibroblasts (LU cells) with a normal diploid karyotype. (nih.gov)
  • 2008) APC/CFzr/Cdh1 promotes cell cycle progression during the Drosophila endocycle. (nih.gov)
  • This cell division process is complex and requires the integration of different pathways such as those involved in cell cycle progression, chromatin modifications, and hormonal signaling. (frontiersin.org)
  • In an early phase TGF-β may act as a tumour suppressor, while later, when cells have become resistant to its anti-mitogenic effects, the role of TGF-β switches towards malignant conversion and progression. (springer.com)
  • Cyclins (regulatory subunits) to form complexes that regulate the progression of the cell cycle. (bdbiosciences.com)
  • p21 can also inhibit cell cycle progression by binding to PCNA and blocking DNA replication. (bdbiosciences.com)
  • Introduction: CDKN1B gene, which encodes a cyclin-dependent kinase (Cdk) inhibitor, regulates the progression throughout G1 to S cell cycle progression. (endocrine-abstracts.org)
  • MMP9 and IGFBP1 Regulate Tumor Immune and Drive Tumor Progression in Clear Cell Renal Cell Carcinoma. (cdc.gov)
  • Mer Tyrosine Kinase (MERTK) modulates liver fibrosis progression and hepatocellular carcinoma development. (cdc.gov)
  • Caused by heterozygous inactivating mutations in the CDKN1B gene (12p13.1-p12) encoding p27, a cyclin-dependent kinase inhibitor that acts as a negative regulator of cell cycle progression. (cdc.gov)
  • Mechanistically, Gal-3 regulates p21 transcription by forming a complex with Sp1, thus blocking cell cycle entry. (nature.com)
  • 13. The Cdk inhibitor p57(Kip2) controls LIM-kinase 1 activity and regulates actin cytoskeleton dynamics. (nih.gov)
  • 15. The cyclin-dependent kinase inhibitor p57Kip2 regulates cell cycle exit, differentiation, and migration of embryonic cerebral cortical precursors. (nih.gov)
  • Rotelli M, Policastro R, Bolling A, Killion A, Weinberg A, Dixon M, Zentner G, Walczak C, Lilly MA, Calvi B. (2019) A Cyclin A-Myb-Aurora B network regulates the choice between mitotic cycles and polyploid endoreplication cycles. (nih.gov)
  • regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. (proteopedia.org)
  • Substituted guanines and pyrimidines were tested as inhibitors of cyclin B1/CDK1 and cyclin A3/CDK2 and soaked into crystals of monomeric CDK2. (rcsb.org)
  • The cyclin-dependent kinase Cdk2 associates with cyclins A, D, and E and has been implicated in the control of the G1 to S phase transition in mammals. (nih.gov)
  • CIP1 encodes a novel 21 kd protein that is found in cyclin A, cyclin D1, cyclin E, and Cdk2 immunoprecipitates. (nih.gov)
  • The structure of CDK2-CyclinA and p27 is determined by crystallography, demonstrating that the inhibitor of p27 stretches at the top of the Cyclin-CDK complex. (wikipedia.org)
  • They can bind and inhibit a broad range of cyclin/Cdk complexes, with a preference for those containing Cdk2 ( 17, 18 ). (aacrjournals.org)
  • Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. (proteopedia.org)
  • NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. (proteopedia.org)
  • Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. (proteopedia.org)
  • We describe the development of highly potent diaminothiazole inhibitors of CDK2 (IC50 = 0.0009-0.0015 muM) from a single hit compound with weak inhibitory activity (IC50 = 15 muM), discovered by high-throughput screening. (proteopedia.org)
  • Zhao J, Kennedy BK, Lawrence BD, Barbie DA, Matera AG, Fletcher JA, Harlow E. NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription. (proteopedia.org)
  • BCL2 family antagonists, CDK inhibitors) are promising new approaches. (springermedizin.de)
  • Once a cell is stopped at a checkpoint due to DNA damage, either the damage is repaired or the cell is induced to perform apoptosis. (wikipedia.org)
  • The p53 protein is an important tumor suppressor that is essential for regulating cell division, senescence, and self-destruction (apoptosis). (medlineplus.gov)
  • No appreciable levels of apoptosis or mitotic figures were observed in the BDO2-treated cells through 96 hr posttreatment. (nih.gov)
  • Adenovirus expressing wild type P53 induces apoptosis in drug resistant human breast cancer cells: a potential in vivo and ex vivo gene therapy approach for Drug Resistant Tumors. (unmc.edu)
  • p53 is a tumor suppressor protein encoded by the TP53 gene that responds to DNA damage by regulating cell-cycle arrest, apoptosis, and senescence. (atcc.org)
  • Induction of apoptosis via reactivation of p53 (e.g., by inhibitors of HDAC or MDM2) and targeting of its downstream pathways (i.e. (springermedizin.de)
  • Changes in cell viability, apoptosis, lactate dehydrogenase release, and cell cycle analysis were measured by cell counting kit-8 assay, annexin V/ propidium iodide staining, and enzyme-linked immunosorbent assay, respectively. (medsci.org)
  • In conclusion, these results indicate that Manu A is a potential to treat human OSCC via cell apoptosis through the downregulation of Sp1. (spandidos-publications.com)
  • To induce apoptosis of cancer cells by targeting the specific signal-transduction pathway could be an effective anticancer therapy. (spandidos-publications.com)
  • Therefore, we investigated whether the Manu A-induced cell apoptosis is related to Specificity protein 1 (Sp1), a transcription factor that binds to a specific DNA sequence, overexpressed in many cancer cells, such as bladder cancer ( 19 ), breast cancer ( 20 , 21 ), pancreatic cancer ( 22 ), gastric cancer ( 23 ) and oral cancer ( 24 ). (spandidos-publications.com)
  • These results demonstrate that Gal-3 is a negative regulator of cell-cycling in HSCs and plays a crucial role in adult hematopoiesis to prevent HSC exhaustion. (nature.com)
  • The AHR is a ligand-dependent transcription factor and key regulator in xenobiotic metabolism and immunity. (frontiersin.org)
  • XL102 is a potent, selective, and orally bioavailable covalent inhibitor of cyclin-dependent kinase 7 (CDK7), which is an important regulator of the cellular transcriptional and cell cycle machinery. (aurigene.com)
  • In the phase 1 trials of the selective cyclin-dependent kinase 4/6 inhibitor palbociclib, 3 patients with unresectable, growing, mature teratoma syndrome achieved prolonged disease stabilization. (nih.gov)
  • Since 2015, the Food and Drug Administration has approved three types of CDK inhibitors (abemaciclib, palbociclib and ribociclib) for CDK 4 and 6: two enzymes that represent the " driving force " of cancerous tumor formation in several different cancer types. (forbes.com)
  • Palbociclib is an oral and selective inhibitor of cyclin dependent kinases (CDK) 4 and 6. (rxwiki.com)
  • Palbociclib is a cyclin-dependent kinase (CDK) 4/6 inhibitor approved for use in patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer (BC). (aspetjournals.org)
  • Total palbociclib uptake was lower in DLD-1 cells than MCF-7 cells both in SCS and in spheroids. (aspetjournals.org)
  • SIGNIFICANCE STATEMENT This study explores palbociclib uptake and efflux in single cell suspension and spheroid models of cancer. (aspetjournals.org)
  • Aurigene presented positive preclinical data demonstrating that XL102 has potent anti-proliferative activity and induces cell death in a large panel of cancer cell lines at the 32nd EORTC-NCI-AACR (ENA) Symposium (Abstract 170) in October 2020. (aurigene.com)
  • These drugs block mammalian target of rapamycin (mTOR), a protein that tells cancer cells to grow and spread. (cancercouncil.com.au)
  • It interacts with 2 tyrosine kinases: fms-like tyrosine kinase-1, Flt-1 (VEGFR-1), and kinase domain-containing region, Flk-1/KDR (VEGFR-2) [2]. (who.int)
  • In the cyclin-dependent kinase (CDK) family or CDK, Cyclin, and CKIs, serine/threonine kinases play an integral role in regulating the eukaryotic cell cycle. (wikipedia.org)
  • Background: Serine/threonine-protein kinase involved in the control of the eukaryotic cell cycle, whose activity is controlled by an associated cyclin. (hatinhibitor.com)
  • controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. (proteopedia.org)
  • Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. (proteopedia.org)
  • Classic TGF-β signaling involves the binding of TGF-β to TGF-β type II receptors (TβRIIs), recruitment of type I receptors (TβRIs), transphosphorylation by TβRII kinase, and the subsequent phosphorylation of receptor regulated (R-)Smad2 and Smad3. (springer.com)
  • Mutations in the CDKN2A gene are found in up to one-quarter of head and neck squamous cell carcinomas (HNSCC). (medlineplus.gov)
  • Mutations in the CDKN2A gene are also associated with melanoma, a type of skin cancer that begins in pigment-producing cells called melanocytes. (medlineplus.gov)
  • CDKN2A gene mutations involved in cancer impair production of functional p16(INK4A) or, less commonly, p14(ARF), which can result in uncontrolled cell growth and tumor formation. (medlineplus.gov)
  • Using the gene expression changes in HPL1A lung airway epithelial cells after exposure to 2,3,7,8-tetrachlorodibenzo- p -dioxin at levels of 0.1, 1.0, and 10.0 nM for 24 hr, a gene expression network was hypothesized and analyzed. (nih.gov)
  • Isolation of a gene encoding a human reduced folate carrier (RFC1) and analysis of its expression in transport-deficient methotrexate-resistant human breast cancer cells. (unmc.edu)
  • ATCC has created gene mutation lists based on the ATCC tumor cell line collection and known mutation information maintained in the Sanger Institute Catalogue of Somatic Mutations in Cancer (COSMIC) database. (atcc.org)
  • The cell lines in each of these panels were selected because they carried a specific mutations or deletion or because they exhibited gene amplification, in the featured gene. (atcc.org)
  • A miR-151 binding site polymorphism in the 3'-untranslated region of the cyclin E1 gene associated with nasopharyngeal carcinoma. (cdc.gov)
  • Gene polymorphisms of cyclin-dependent kinase inhibitor and matrix metalloproteinase-9 in Sudanese patients with esophageal squamous cell carcinoma. (cdc.gov)
  • MEN 4 is caused by an inactivating mutation of the CDKN1B gene, which codes for the cyclin dependent kinase inhibitor 1B protein, also known as p27 or p27KIP1. (msdmanuals.com)
  • Cutaneous squamous cell carcinoma (SCC) is one of the most frequent malignancies in humans and academia as well as public authorities expect a further increase of its incidence in the next years. (frontiersin.org)
  • However, the anticancer effects of Manu A on oral squamous cell carcinoma (OSCC) have not been reported. (spandidos-publications.com)
  • Oral squamous cell carcinoma (OSCC) which occurs in the lining of the epithelial cell represents approximately 95% of head and neck cancer and is the sixth most common malignant neoplasm worldwide ( 3 - 5 ). (spandidos-publications.com)
  • Matrix metalloproteinase 1, 3, and 9 polymorphisms and esophageal squamous cell carcinoma risk. (cdc.gov)
  • Although one molecule of p21 is sufficient to inhibit cyclin/Cdk complexes ( 22 ), Cip/Kip CKIs have been detected in active cyclin D/Cdk4 complexes ( 24 - 27 ). (aacrjournals.org)
  • p21 was shown to stabilize interactions between Cdk4 and cyclin D and promote the formation of active complexes in a concentration-dependent manner ( 27 ). (aacrjournals.org)
  • CDK4 and CDK6 normally stimulate the cell to continue through the cycle and divide. (medlineplus.gov)
  • Researchers at the National Center for Advancing Translational Sciences (NCATS) recently identified compounds that potentially can be used to inhibit Zika virus replication and reduce its ability to kill brain cells. (nih.gov)
  • These compounds were effective either in inhibiting the replication of Zika or in preventing the virus from killing brain cells. (nih.gov)
  • For example, emricasan prevents cell death, and niclosamide and the nine CDK inhibitors stop the virus' replication. (nih.gov)
  • The team also found that emricasan, when combined with one of the CDK inhibitors, prevented both cell death and virus replication. (nih.gov)
  • 2007) The cyclin-dependent kinase inhibitor Dacapo promotes replication licensing during Drosophila endocycles. (nih.gov)
  • activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. (proteopedia.org)
  • It may work by inhibiting cell growth and DNA replication. (rxwiki.com)
  • It acts as a tumor suppressor and when the protein is lost, cells can undergo unscheduled replication, which may eventually lead to cancer. (msdmanuals.com)
  • Furthermore, we show that the mechanism of transcriptional activation of these cyclin dependent kinase inhibitor genes by MEOX1 and MEOX2 is distinct. (nih.gov)
  • Somatic mutations in other genes involved in cell growth are also needed for a melanoma to develop. (medlineplus.gov)
  • Identification of the retinoid-responsive genes in the TCDD microarray analyses suggested a functional relationship between AhR activation and retinoid homeostasis and/or signaling in the human lung epithelial cells. (nih.gov)
  • Our scientists pursue every aspect of cancer research-from exploring the biology of genes and cells, to developing immune-based treatments, uncovering the causes of metastasis, and more. (mskcc.org)
  • The tumor cell panels in the genetic alteration collection are organized around genes that have important implications for cancer research. (atcc.org)
  • For validation of potential cancer driver genes, functional profiling and molecular profiling of subtype-specific cancer cell lines, and testing small molecules or biologics for cancer drug development. (atcc.org)
  • It is challenging to study the role of these cells in these age-related brain changes in humans because senescent cells are much fewer in number than healthy cells, are often scattered throughout an organ or tissue, and do not all express the same genes. (nih.gov)
  • To identify senescent cells, the researchers measured the levels of RNA from three groups of genes involved in processes that are hallmarks of senescence, including inflammation, a halt in cell division, and the body's response to stress. (nih.gov)
  • If cell mutations surpass the cell cycle checkpoints during cell cycle regulation, it can result in various types of cancer. (wikipedia.org)
  • 20. Cyclic changes in the expression of p57(kip2) in human endometrium and its regulation by steroid hormones in endometrial stromal cells in vitro. (nih.gov)
  • Hormone dependent regulation of BRCA1 in human breast cancer cells. (unmc.edu)
  • In both gametophytes, the retinoblastoma-related protein (RBR) plays a key role in the regulation of the cell cycle by inhibiting cell cycle entry through repressing E2F transcription factors. (frontiersin.org)
  • KISQALI FEMARA CO-PACK, a co-packaged product containing ribociclib, a kinase inhibitor, and letrozole, an aromatase inhibitor, is indicated as initial endocrine-based therapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. (nih.gov)
  • To overcome this hurdle, characterization of the stem-cell niche is important for understanding the molecular mechanisms whereby stem cells differentiate or self-renew. (nature.com)
  • Molecular Biology of the Cell. (nih.gov)
  • At the molecular level, in fact, a gradual weakening of the cellular processes regulating cardiovascular homeostasis occurs in aging cells. (hindawi.com)
  • Activation of the cellular senescence genetic program prompts a series of molecular changes, mostly affecting cell cycle, extracellular matrix (ECM), secretion of growth factors, and inflammatory mediators. (hindawi.com)
  • For this new study, the scientific team developed a novel approach that combines molecular biology and advanced statistical methods to identify and analyze senescent cells in the donated brains of people who died with Alzheimer's. (nih.gov)
  • Major advances in the molecular characterization of T-PLL during recent years have stimulated translational studies on potential vulnerabilities of the T-PLL cell. (springermedizin.de)
  • We found that the human FBR is mediated by immune-cell-specific RAC2 mechanotransduction signalling, independently of the chemistry and mechanical properties of the implant, and that a pathological FBR that is human-like at the molecular, cellular and tissue levels can be induced in mice via the application of human-tissue-scale forces through a vibrating silicone implant. (stanford.edu)
  • Senescence, the state of permanent cell cycle arrest, has been associated with endothelial cell dysfunction and atherosclerosis. (nih.gov)
  • We compared the ability of MEOX1 and MEOX2 to activate p21(CIP1/WAF1) and p16(INK4a) expression and induce endothelial cell cycle arrest. (nih.gov)
  • In addition, increased expression of either of the MEOX homeodomain transcription factors leads to cell cycle arrest and endothelial cell senescence. (nih.gov)
  • The cyclin-dependent kinase inhibitor p21 is induced by both p53-dependent and -independent mechanisms following stress, and induction of p21 may cause cell cycle arrest. (aacrjournals.org)
  • 19. BMP2 and BMP6 control p57(Kip2) expression and cell growth arrest/terminal differentiation in normal primary human epidermal keratinocytes. (nih.gov)
  • Acute exposure of human lung cells to 1,3-butadiene diepoxide results in G1 and G2 cell cycle arrest. (nih.gov)
  • Both G1 and G2 arrest were prolonged and only a very small percentage of BDO2-treated cells were eventually able to replicate. (nih.gov)
  • Increased nuclear localization of both p53 and p21(cip1) was observed in BDO2-treated cells, suggesting that the cell cycle arrest was p21(cip1)-mediated. (nih.gov)
  • Effects of adenovirus-mediated p16INK4A expression on cell cycle arrest are determined by endogenous p16 and Rb status in Human Cancer Cells. (unmc.edu)
  • It has been previously demonstrated that the atypical BC human cell line NCI-H720 is sensitive to everolimus (E), an m-TOR inhibitor, in terms of cell viability reduction, with a G0 cell-cycle arrest and a Cyclin D1 protein reduction. (endocrine-abstracts.org)
  • A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. (bvsalud.org)
  • Development of Highly Potent and Selective Diaminothiazole Inhibitors of Cyclin-Dependent Kinases. (proteopedia.org)
  • In vivo, chronic treatment with the non-selective antidepressant imipramine as well as the norepinephrine-selective reuptake inhibitor desipramine or the serotonin-selective reuptake inhibitor fluoxetine all decrease p21 expression, and this was associated with increased neurogenesis. (blogspot.com)
  • CDK inhibitors are a type of cancer treatment - a drug such as the ones given during chemotherapy - to block this activity, inhibit this cell division, and slow the growth and spread of cancer cells. (forbes.com)
  • However, the mechanisms underlying this phenomenon have not been fully clarified.Aim: The aim of our study is to investigate the mechanisms of resistance to mTOR inhibitors in BC cells. (endocrine-abstracts.org)
  • We aimed to examine whether EPA could protect vascular endothelial cells under stress conditions against stress-induced accelerated senescence (SIAS). (medsci.org)
  • Against human tumor cells, NU2058 and NU6027 were growth inhibitory in vitro (mean GI50 values of 13 +/- 7 microM and 10 +/- 6 microM, respectively), with a pattern of sensitivity distinct from flavopiridol and olomoucine. (rcsb.org)
  • CKIs help promote the specific inhibitory signals that contain the cell from entering the S phase. (wikipedia.org)
  • 4. The multiple roles of the cyclin-dependent kinase inhibitory protein p57(KIP2) in cerebral cortical neurogenesis. (nih.gov)
  • the activation of these enzymes helps the cell divide. (forbes.com)
  • Reversible transcriptional activation of mdr 1 by sodium butyrate treatment of human colon cancer cells. (unmc.edu)
  • Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. (proteopedia.org)
  • FBRs to such elevated extrinsic forces in the mice were also mediated by the activation of Rac2 signalling in a subpopulation of mechanoresponsive myeloid cells, which could be substantially reduced via the pharmacological or genetic inhibition of Rac2. (stanford.edu)
  • These CDK inhibition and chemosensitivity data indicate that the distinct mode of binding of NU2058 and NU6027 has direct consequences for enzyme and cell growth inhibition. (rcsb.org)
  • they were originally discovered in the 1970s when Endo and Kuroda identified an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which they named mevastatin. (medscape.com)
  • These observations suggest that the biotin administration ameliorates abnormal glucose metabolism in diabetic patients, presumably by enhancing the activity of the biotin-dependent enzyme, pyruvate carboxylase, with a subsequent promotion of glucose utilization for the entry into the tricarboxylic acid cycle. (researchgate.net)
  • TGF-β is a very potent growth inhibitor of primary human mammary epithelial cells. (springer.com)
  • ALAMEDA, Calif. - December 7, 2020 - Exelixis, Inc. (Nasdaq: EXEL) and Aurigene today announced that Exelixis has exercised its exclusive option for Aurigene's novel CDK7 inhibitor under the companies' July 2019 agreement. (aurigene.com)
  • While it is commonly accepted as an aging-related phenomenon, senescence might happen also during the embryonic development with the biological meaning of replacing transient structures or specific cell types with other ones [ 3 - 5 ]. (hindawi.com)
  • Scientists working in basic, translational, and clinical cancer metabolism research are invited to join the Academy in New York on April 17th to discuss the intersection between cell signaling and metabolism. (nyas.org)
  • Mechanical stimulation from the surrounding tissue activates mitochondrial energy 1 metabolism in differentiating germ cells. (nih.gov)
  • 5. Downregulation of p57kip² promotes cell invasion via LIMK/cofilin pathway in human nasopharyngeal carcinoma cells. (nih.gov)
  • By screening for mutants that are sensitive to benzyl alcohol, we show that the bifunctional cell wall synthase PonA2 promotes membrane partitioning and cell growth during recovery from benzyl alcohol exposure. (elifesciences.org)
  • Active cell wall polymerization promotes de novo membrane partitioning and the completed cell wall polymer helps to maintain membrane partitioning. (elifesciences.org)
  • Atherosclerosis and heart failure are particularly correlated with aging-related cardiovascular senescence, that is, the inability of cells to progress in the mitotic program until completion of cytokinesis. (hindawi.com)
  • Mitotic cells might undergo senescence by failing to replicate. (hindawi.com)
  • Only one of them, the functional megaspore, continues its development and goes through three mitotic divisions forming a mature embryo sac composed of eight nuclei and seven cells: three antipodal cells, two medial polar nuclei, and one egg cell surrounded by two synergids ( Mansfield and Briarty, 1991 ). (frontiersin.org)
  • The cyclin dependent kinase inhibitors p21(CIP1/WAF1) and p16(INK4a) govern the G(1)/S cell cycle checkpoint and are essential for determining whether a cell enters into an arrested state. (nih.gov)
  • 3. Contrasting roles of p57(KIP2) and p21(WAF1/CIP1/SDI1) in transplanted human and bovine adrenocortical cells. (nih.gov)
  • Effects of cell cycle, wild type p53 and DNA damage on p21CIPI/WafI expression in human breast epithelial cells. (unmc.edu)
  • The present study investigates the functional significance of Cdk5 in forming and maintaining cell-cell stability in corneal epithelial cells. (molvis.org)
  • A Cdk5-deficient human corneal limbal epithelial cell line was generated by lentiviral transduction of small hairpin RNA specific for Cdk5 (shCdk5-HCLE cells). (molvis.org)
  • A blasticidin-inducible vector for expression of Cdk5-specific short hairpin RNA (ShCdk5) was generated by recombination and packaged into non-replicative lentiviral particles for transduction of human corneal limbal epithelial (HCLE) cells. (molvis.org)
  • Examining the effect of Cdk5 on E-cadherin containing epithelial cell-cell adhesions using a corneal epithelial cell line (HCLE), we found that Cdk5 and Cdk5 (pY15) coimmunoprecipitate with E-cadherin and Cdk5 (pY15) colocalizes with E-cadherin at cell-cell junctions. (molvis.org)
  • Sacituzumab govitecan (SG) is a first-in-class antibody-drug conjugate with an SN-38 payload targeting trophoblast cell-surface antigen 2, an epithelial antigen expressed in breast cancer. (medscape.com)
  • It has steered to various other fields of study such as developmental biology, cell biology and cancer research. (wikipedia.org)
  • Role in cancer: Cyclin-dependent kinase inhibitors (CKIs) mutants are frequent in human cancers. (wikipedia.org)
  • When there is uncontrolled cell growth, it can lead to cancer cells due to the inactivation of the CKIs. (wikipedia.org)
  • In the current review, we discuss the role of p21 in regulating cell death and the potential relevance of its expression in cancer. (aacrjournals.org)
  • Without one of these tumor suppressors, cells can grow and divide unchecked, leading to the development of cancer. (medlineplus.gov)
  • Despite these CDK inhibitors' relatively limited use, one article notes that their development is "arguably one of the most clinically important discoveries" for patients with HR+ ERBB2- breast cancer patients. (forbes.com)
  • Treating them with a combination of hormone therapy and a CDK 4/6 inhibitor can give them more time ( roughly 12 months ) before the cancer spreads and higher survival rates overall than those treated with hormone therapy only. (forbes.com)
  • Cancer cells that aren't killed off by the prior lines of treatment can develop resistance to those very same treatments, limiting their effectiveness in the future. (forbes.com)
  • In order to fight cancer, researchers require an array of authenticated tumor cells to understand the mechanisms that drive carcinogenesis and metastasis, and to test new therapies. (atcc.org)
  • ATCC offers a wide variety of cancer cell lines for use in research related to cancer genetics, early detection methods, and effective treatment of disease. (atcc.org)
  • ATCC Tumor Cell Panels are powerful tools to accelerate your discoveries in cancer research, compound screening, biomarker selection, pathway analysis, and targeted therapeutic development. (atcc.org)
  • The RAS genetic alteration panel is composed of 10 select cell lines, derived from a variety of common human cancer types. (atcc.org)
  • These are called systemic therapies because they can reach cancer cells almost anywhere in the body. (cancer.org)
  • Even in the early stages of breast cancer, cancer cells may break away from the main breast tumor and begin to spread. (cancer.org)
  • They lock onto a protein on the surface of cells or surrounding tissues to affect how cancer cells grow and survive. (cancercouncil.com.au)
  • High levels of the protein HER2 cause cancer cells to grow uncontrollably. (cancercouncil.com.au)
  • Some targeted therapy drugs destroy the HER2 positive cancer cells, or reduce their ability to divide and grow. (cancercouncil.com.au)
  • Without this signal, the cancer cells may die. (cancercouncil.com.au)
  • These drugs block poly (ADP-ribose) polymerase (PARP), a protein that repairs damaged DNA in cancer cells. (cancercouncil.com.au)
  • These drugs block cyclin-dependent kinase (CDK) from sending signals that tell cancer cells to grow, multiply and spread. (cancercouncil.com.au)
  • TGF-β stimulates cell invasion and modifies the microenvironment to the advantage of cancer cells. (springer.com)
  • One of the genetic and biological factors in breast cancer biology that is widely studied is the secreted cell to cell signaling molecule, transforming growth factor-β (TGF-β). (springer.com)
  • The metastasis of breast cancer cells to remote tissues is not a random process. (springer.com)
  • The preclinical data generated to date for XL102 demonstrate that this novel CDK7 inhibitor is orally available and has significant potential to improve care and outcomes for patients with diverse cancer indications, including breast cancer, prostate cancer, leukemia, and lymphoma. (aurigene.com)
  • 10. [The role of cyclin-dependent kinase inhibitors in hyperplasia and hypertrophy of vascular smooth muscle cells]. (nih.gov)
  • Multiple endocrine neoplasia, type 4 (MEN 4) is an autosomal dominant syndrome characterized by adenomas and sometimes hyperplasia of the parathyroid glands and tumors of the pancreatic islet cells and/or pituitary gland. (msdmanuals.com)
  • A la I Conferència i Taller Internacional sobre diferenciació dels antígens leucocitaris humans , celebrada a París el 1982, fou aprovada la terminologia CD (cúmul o grup de diferenciació [18] o cluster of differentiation en anglès). (wikipedia.org)
  • Non-melanoma skin cancers, in particular basal cell carcinoma and SCC, are among the most frequent malignancies in humans ( 1 - 3 ). (frontiersin.org)
  • Pathologies, as atherosclerosis, cardiac fibrosis, and cardiomyopathy, are often linked to the failure of cardiovascular tissue cells to reenter the cell cycle, namely, senescence, due to endogenous or exogenous causes. (hindawi.com)
  • [ 16 ] Because SN-38 is a membrane-permeable free molecule released in the tumor microenvironment, it may elicit antitumor effects in adjacent non-Trop-2-expressing tumor cells (bystander effect). (medscape.com)
  • Alterations in the retinoblastoma pathway in germ cell tumors (GCTs) have been described. (nih.gov)
  • Besides the canonical TGF-β/Smad pathway, TGF-β can directly activate non-Smad signaling pathways [ 6 , 7 ], including the mitogen activated protein (MAP) kinases. (springer.com)
  • This pathway functions in regulating many fundamental processes required for cell viability. (embl.de)
  • Aurigene is focused on precision-oncology, oral immune checkpoint inhibitors, and the Th-17 pathway. (aurigene.com)
  • This review will focus on the cardiovascular pathologies correlated to senescence, the effect of aging on the cardiac endogenous resources of stem cells, and the potential strategies of regenerative medicine to be applied to maintain the heart younger and healthier. (hindawi.com)
  • Cellular senescence is a process in which various stressors permanently stop cell division, resulting in cell changes that appear as senescent-associated secretory phenotype (SASP) ( 2 ). (medsci.org)
  • Mechanoregulation of Notch signaling activity in endothelial cells and its influence on angiogenic sprouting. (uni-muenchen.de)
  • Mechanical communication of endothelial cells and its influence on the organization of cellular structures. (uni-muenchen.de)
  • Actin-dependent mechanosensing in endothelial cells: regulatory aspects and targeting potential. (uni-muenchen.de)
  • Artificial angiogenesis: characterization of endothelial cell migration in three-dimensional model systems. (uni-muenchen.de)
  • Models for angiogenesis on micro-structured surfaces: a novel view on endothelial cell biology. (uni-muenchen.de)
  • Cyclin-dependent kinase 5 in endothelial cell migration: Elucidating regulatory mechanisms upstream of Cdk5 and evaluating novel Cdk inhibitors as anti-angiogenic drugs. (uni-muenchen.de)
  • Anti-angiogenic effects of Cyclin dependent kinase inhibitors: Novel function of Cyclin dependent kinase 5 in endothelial cell migration. (uni-muenchen.de)
  • Influence of Ginkgo biloba extract EGb 761 on signaling pathways in endothelial cells. (uni-muenchen.de)
  • Cultured human umbilical vein endothelial cells (HUVECs) were exposed to H 2 O 2 as oxidative stress and a high glucose concentration with palmitate as a glucolipotoxic condition. (medsci.org)
  • The senescent neurons also had high levels of a protein called cyclin-dependent kinase inhibitor 2D ( CDKN2D/ p19), which helps control whether a cell divides. (nih.gov)
  • These drugs target a protein called CD20 found on some B-cell leukaemia and non-Hodgkin lymphomas. (cancercouncil.com.au)
  • Conditional overexpression of Gal-3 in mouse HSCs under the transcriptional control of Tie2 or Vav1 promoters (Gal-3 Tg) causes cell cycle retardation via induction of p21. (nature.com)
  • Three lead compounds, emiracsan, niclosamide and a CDK inhibitor known as PHA-690509, were identified as reducing neuronal cell death caused by Zika virus infection. (nih.gov)
  • These three CKIs contain a conserved region of sequence at the NH 2 terminus that is required and sufficient for the inhibition of cyclin/Cdk complexes, whereas the COOH terminal regions are variable in length and function ( 12, 14 - 16 ). (aacrjournals.org)
  • Moreover, Cdk5 inhibition induced N-cadherin expression and formation of N-cadherin/p120 complexes in HCLE cells. (molvis.org)
  • p21 has also shown to be a component of active cyclin-cdk complexes, suggesting that p21-containing complexes may shift between active and inactive states through changes in p21 content. (bdbiosciences.com)
  • These checkpoints' cell cycle blocks at both the G1/S and G2/M checkpoints are consistent with the inhibition profile of the enzymes. (wikipedia.org)