Cyclin-Dependent KinaseKinaseDownstreamProteinsEnhancing p21 expressionInhibitionPAK1InhibitorCIP1MRNAInhibitors p21ApoptosisGenesApoptotic pathwaysArrestMDM2PhosphorylationMTORActivationExpressionProgressionSenescenceActivatesIntrinsicIncreasesNegativelyPI3KCellularAccumulationGeneMolecularAntigenCell cycleNeoplasmsInhibitsInsulinInflammatoryIntracellularHumanResponseRoleCells

Cyclin-Dependent Kinase2

• Treatment with the stress agent prostaglandin A 2 (PGA 2 ) induces expression of the cyclin-dependent kinase inhibitor p21. (johnshopkins.edu)
• Regulation of the activation of the Fanconi anemia pathway by the p21 cyclin-dependent kinase inhibitor. (uri.edu)

Kinase22

• Mutations in K-Ras and B-Raf activate the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathways. (biomedcentral.com)
• The p21 activated kinase (PAK) family of proteins has been identified as a novel target for cancer therapies [ 7 ]. (biomedcentral.com)
• Here, we present evidence that p21 expression increases through PGA 2 -triggered stabilization of the p21 mRNA and further show that these events require the mitogen-activated protein (MAP) kinase ERK. (johnshopkins.edu)
• We have identified a novel pathway that directs Lyn/Src family tyrosine kinase signals to the invadopodia to regulate sarcoma cell invasion via the molecule AFAP-1-like-1 (AFAP1L1), a new member of the AFAP (actin filament-associated protein) family. (nature.com)
• AFAP1L1 intersects several invadopodia pathway components through its multiple domains and motifs, including the following (i) pleckstrin homology domains that bind phospholipids generated at the plasma membrane by phosphoinositide 3-kinase, (ii) a direct filamentous-actin binding domain and (iii) phospho-tyrosine motifs (pY136 and pY566) that specifically bind Vav2 and Nck2 SH2 domains, respectively. (nature.com)
• Through its interaction with Vav2, AFAP1L1 regulates Rac activity and downstream control of PAK1/2/3 (p21-activated kinases) phosphorylation of myosin light chain (MLC) kinase and MLC2. (nature.com)
• These data define a novel pathway that directs Lyn/Src family tyrosine kinase signals to sarcoma cell invadopodia through specific recruitment of Vav2 and Nck2 to phosphorylated AFAP1L1, to control cell migration and invasion. (nature.com)
• ACT‑3 significantly reduced the expression levels of cyclin D1 and cyclin‑dependent kinase 4, and upregulated the expression levels of p21 and p53. (iasp-pain.org)
• Additionally, ACT‑3 significantly increased autophagic cell death by inhibiting the serine‑threonine kinase/mammalian target of the rapamycin pathway. (iasp-pain.org)
• One of the well established Rho-kinase-mediated signaling pathways is the phosphorylation of myosin light chain (MLC) and its counteracting MLC phosphatase. (uni-muenchen.de)
• Rho-kinase regulates a second pathway that involves activation of LIM-kinases (LIMKs) and subsequent phosphorylation and inactivation of cofilin, an actin dynamizing protein. (uni-muenchen.de)
• The signaling pathway Rho-kinase/LIMKs/cofilin phosphorylation during platelet activation and the question, how the phosphorylation of cofilin affects the actin dynamics underlying platelet activation, has not previously been studied. (uni-muenchen.de)
• LIMK-1 can be activated by Rho-kinase as well as by p21-activated kinases (PAKs). (uni-muenchen.de)
• Inhibition of the Rho-kinase/LIMK-1 pathway unmasked cofilin dephosphorylation suggesting that during shape change the simultaneous activation of a cofilin phosphatase counteracts the effect of LIMK-1 for phosphorylating cofilin. (uni-muenchen.de)
• Since the kinetics of cofilin phospho-cycle was similar during secretion and platelet aggregation in LPA- and thrombin-stimulated cells, I propose a general two-step regulatory process for cofilin phospho-cycle underlying primarily secretion, and subsequently platelet aggregation: dephosphorylation by a cofilin phosphatase and then rephosphorylation by the Rho-kinase/LIMK-1 pathway. (uni-muenchen.de)
• Finally, IGF‑1R protein, phosphoinositide 3‑kinase/Akt signaling pathway‑associated proteins and cyclin pathway‑associated proteins were differentially expressed between miR‑497‑overexpressing cells and miR-497-silenced cells. (spandidos-publications.com)
• P21-activated kinase 3 (PAK3) is a serine/threonine protein kinase, and PAK3 affects the EMT, proliferation, metastasis and invasion of HCC. (jcancer.org)
• SnCs exhibit irreversible growth arrest accompanied by increased expression of cyclin-dependent kinase inhibitors (CDKi) such as p16 INK4a , and p21 Cip1 , accumulation of DNA damages, and secretion of diverse bioactive molecules known as the senescence-associated secretory phenotype (SASP). (aging-us.com)
• Transcriptional activation of p21(waf1/cip1) by alkylphospholipids: role of the mitogen-activated protein kinase pathway in the transactivation of the human p21(waf1/cip1) promoter by Sp1. (conicet.gov.ar)
• Moreover, we showed that perifosine activates the mitogen-activated protein/extracellular signal-regulated kinase pathway, and this activation promotes the phosphorylation of Sp1 in known mitogen-activated protein kinase residues (threonine 453 and 739), thereby leading to increased Sp1 binding and enhanced p21(waf1/cip1) transcription. (conicet.gov.ar)
• The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)
• Similarly, depletion in the STRIPAK component STRIP1 affects activation of GCKIII kinases and cell cycle disruption through elevated expression of cyclin dependent kinase inhibitors p21 and p27, enhanced levels of which lead to a protective effect from therapeutic treatments and increased proliferation. (lu.se)

Downstream4

• After receptor activation, the alpha- and beta-gamma-subunits of G protein dissociate to activate diverse downstream pathways resulting in cellular polarization and actin reorganization. (genome.jp)
• IRE1α-XBP1 were essential for expansion of activated mouse and human NK cells and are situated downstream of the mammalian target of rapamycin signaling pathway. (cancerindex.org)
• However, the pathway downstream NDRG1, involving p21 and c8/18, regulating cell cycle progression and DNA synthesis is unfunctional. (scirp.org)
• In response to DNA-damaging agents, the wild-type p53-activated fragment 1 (WAF1 also known as p21) is an important downstream effector in the p53-specific growth arrest pathway. (lu.se)

Proteins8

• Ribosomal proteins (RPs) play important roles in modulating the MDM2-p53 pathway. (elifesciences.org)
• it still remains to be determined if there are more proteins that can regulate the RPs-MDM2-p53 pathway. (elifesciences.org)
• In particular, we will discuss the modifications in intrinsic and extrinsic apoptotic pathways caused by proteins encoded by HPV early genes. (mdpi.com)
• This gene encodes a family member of serine/threonine p21-activating kinases, known as PAK proteins. (antikoerper-online.de)
• A central step in the regulation of the activation of the FA-BRCA pathway is the mono-ubiquitination of the FANCD2 (and FANCI) proteins. (uri.edu)
• Histological changes at the tubular level, progress of cell senescence, and the expression of Rb, p21, and/or p53 proteins in tubular cells were studied at different moments in time after IRI. (techscience.com)
• In mice of both genotypes, cell senescence was correlated with the expression levels of p53, p21, and Rb proteins. (techscience.com)
• There are suggestions that G protein-coupled receptor (GPCR) second messenger pathways are altered during ageing, rather than the receptor proteins themselves. (bvsalud.org)

Enhancing p21 expression1

• RNA interference-based knockdown of HuR abundance further served to demonstrate the contribution of HuR-mediated p21 mRNA stabilization toward enhancing p21 expression after PGA 2 treatment. (johnshopkins.edu)

Inhibition3

• Interestingly, although inhibition of the ERK pathway did not prevent the PGA 2 -triggered increase in cytoplasmic HuR, it did impair the formation of endogenous and in vitro [HuR-p21 mRNA] complexes and further prevented the PGA 2 -mediated stabilization of the p21 mRNA, suggesting that ERK-mediated events were required for binding HuR to the p21 mRNA and preventing its decay. (johnshopkins.edu)
• It further inhibited cell-cycle progression in the G1 phase by four different mechanisms: rapid downregulation of cyclin D1, induction of Chk2 with simultaneous downregulation of Cdc25A, induction of the Cdk-inhibitor p21 Cip/Waf and inhibition of ribonucleotide reductase activity resulting in reduced dCTP and dTTP levels. (nature.com)
• Anticancer effects of the HDAC inhibitor, 3β,6β‑dihydroxyurs‑12‑en‑27‑oic acid, in MCF‑7 breast cancer cells via the inhibition of Akt/mTOR pathways. (iasp-pain.org)

PAK11

• Activated PAK1 enhances cell survival and migration via the AKT pathway, and stimulates transformation through the Ras/Raf/ERK/MAPK pathway. (biomedcentral.com)

Inhibitor3

• miR-128-5p targets the tissue inhibitor of metalloproteinases (TIMPs), silent information regulator 2 (SIRT2), peroxisome proliferator-activated receptor (PPAR), and p21 genes, which are linked to the behaviours of VSMCs. (hindawi.com)
• The inhibitor increased p21, p27, and SM22ɑ expression and repressed the migration, phenotypic transformation, and proliferation of VSMCs. (hindawi.com)
• Several studies have shown that miRNAs play multiple roles in the phenotypic transformation, migration, and proliferation of VSMCs by inhibiting ERK1/2 activation [ 11 , 12 ], partly by regulating the tissue inhibitor of metalloproteinases (TIMPs)-MMPs and p21-cyclins interactions [ 13 - 18 ]. (hindawi.com)

CIP15

• We have shown previously that perifosine induces p21(waf1/cip1) in a p53-independent fashion and that induction of p21(waf1/cip1) is required for the perifosine-induced cell cycle arrest because cell lines lacking p21(waf1/cip1) are refractory to perifosine. (conicet.gov.ar)
• In this report, we investigated the mechanism by which perifosine induces p21(waf1/cip1) protein expression. (conicet.gov.ar)
• We observed that perifosine induces the accumulation of p21(waf1/cip1) mRNA without affecting p21(waf1/cip1) mRNA stability. (conicet.gov.ar)
• Using several p21(waf1/cip1) promoter-driven luciferase reporter plasmids, we observed that perifosine activates the 2.4-kb full-length p21(waf1/cip1) promoter as well as a p21 promoter construct lacking p53-binding sites, suggesting that perifosine activates the p21(waf1/cip1) promoter independent of p53. (conicet.gov.ar)
• Mutations in each particular Sp1 site block perifosine-induced p21(waf1/cip1) expression. (conicet.gov.ar)

MRNA3

• Binding experiments using either endogenous p21 mRNA or in vitro-labeled p21 transcripts revealed a specific PGA 2 -dependent association of the p21 mRNA with the RNA-binding protein HuR. (johnshopkins.edu)
• Collectively, our results indicate that PGA 2 stabilizes the p21 mRNA through an ERK-independent increase in cytoplasmic HuR levels and an ERK-dependent association of HuR with the p21 mRNA. (johnshopkins.edu)
• In addition, the p21 mRNA level was elevated in 1,4-BQ-treated cells, suggesting that human CD34(+) cells utilize the p53 pathway in response to 1,4-BQ-induced DNA damage. (rti.org)

Inhibitors p211

• Expression of cell cycle inhibitors, P21 and P27, and activation of apoptosis executer enzyme, caspase-3, were also induced by TCEE. (hindawi.com)

Apoptosis2

• Thus, the activated ERK pathway played an important role in cell cycle arrest and apoptosis via ERK‑dependent induction of p21 in MCF‑7 cells. (iasp-pain.org)
• TP53 activates the expression of genes involved in apoptosis, cell cycle regulation (p21), and MDM2. (medscape.com)

Genes2

• Laverne is a handy bioinformatics tool to help facilitate scientific exploration of related genes, diseases and pathways based on co-citations. (novusbio.com)
• The protein products of these genes are thought to act cooperatively in a pathway, the FA-BRCA pathway, to repair DNA damage and prevent cellular transformation. (uri.edu)

Apoptotic pathways1

• NF-kB is central to many immune, inflammatory, and apoptotic pathways. (medscape.com)

Arrest5

• It specifically negatively regulates the PI3K-AKT signaling pathway to induce cell cycle arrest. (medscape.com)
• However, WSC induced cell cycle arrest and cellular senescence mediated by the p53-p21 pathway. (nih.gov)
• Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. (kegg.jp)
• In the mating pheromone response pathway, G-protein-mediated growth arrest induced by cell contact has been confirmed, while GNG7 may be involved in this process to prevent growth arrest in multicellular organisms and control cell proliferation [ 19 ]. (biomedcentral.com)
• Activation of p21 or p16 therefore causes cell cycle arrest. (medscape.com)

MDM21

• KLF6 downregulation enhances MDM2 gene expression that deregulates the p53 pathway [ 9 ]. (medsci.org)

Phosphorylation1

• The effects of A 2A R activation on lysosomal calcium are not mediated by the cAMP/PKA pathway but they appear to involve the phosphorylation of ERK1/2. (jneurosci.org)

MTOR2

• Further studies showed that UASR1 activated AKT and AKT-mediated mTOR signaling pathway to stimulate cell proliferation and growth. (jcancer.org)
• Taken together, our data suggest that UASR1 plays an oncogenic role in breast cancer cells through activation of the AKT/mTOR signaling pathway, being a novel RNA oncogene. (jcancer.org)

Activation5

• A study has demonstrated that activation of the peroxisome proliferator-activated receptor g coactivator 1-α (PGC-1α)/ERRα pathway increases VEGF expression and angiogenesis in endothelial cells, which suggests that ERRα may be involved in the pathogenesis of DR ( 10 ). (spandidos-publications.com)
• Furthermore, the activation of p53-Rb signaling pathway may play a vital role in tubular cell senescence induced by IRI. (techscience.com)
• The minimal p21 promoter region required for perifosine-induced p21 promoter activation contains four consensus Sp1-binding sites. (conicet.gov.ar)
• As a result of such mutations, p21-RAS becomes locked in its active conformation, leading to the constitutive activation of the protein and tumor development. (medscape.com)
• Over-expression of COMP leads to activation of Notch which affects both Wnt/β-catenin and AKT pathways, already affected by COMP. (lu.se)

Expression11

• The expression of E6 and E7 not only inhibits the tumor suppressors p53 and Rb, but also alters additional signalling pathways. (genome.jp)
• The miR-128-5p mimic promoted the migration and proliferation of VSMCs and suppressed p21, p27, and SM22ɑ expression. (hindawi.com)
• miR-128-5p directly targeted the 3′UTR-binding sequences of the p21 gene, negatively regulated p21 expression, and supported the proliferation of VSMCs. (hindawi.com)
• This resulted in over-expression of NDRG1, which in turn markedly up regulated two differentiation markers of the prostate tissue, p21 and cytokeratin 8/18. (scirp.org)
• These results revealed that NDRG1 is functional in prostate cancer cells and able to induce expression of differentiation factors through p53 independent pathway. (scirp.org)
• KLF6 functions as a tumor suppressor gene and increases p21 expression via p53-independent pathway [ 3 ]. (medsci.org)
• Finally, we found that PAK3 regulated EMT-related molecule expression and EMT-related TGF-β/smad signaling pathway. (jcancer.org)
• In breast cancer patients, it is unclear whether measuring p53, mdm-2, or p21 expression provides information on how patients will respond to chemotherapy. (lu.se)
• p53, mdm-2, p21, and mib-1 expression were assessed by immunohistochemical methods in primary tumors derived from 134 patients who took part in a randomized multicenter trial comparing docetaxel to sequential methotrexate and 5-fluorouracil (MF) in advanced breast cancer. (lu.se)
• p53, mdm-2, p21, and mib-1 expression were not significantly associated with response to chemotherapy, time to progression, or overall survival in the whole patient population or in the docetaxel group. (lu.se)
• Interestingly, tumors with both negative mdm-2 and p21 expression, irrespective of p53 status, had a high response rate to docetaxel but no response to MF. (lu.se)

Progression1

• Furthermore, poorer prognosis in cancer patients who display a glycolytic phenotype characterized by metabolic alterations, such as obesity and diabetes, is now well established, providing another link between metabolic pathways and cancer progression. (springer.com)

Senescence1

• To investigate the course of tubular cell senescence and expressions of p53, p21, and Rb during the late phase of ischemia/reperfusion (IRI) in the kidney, and assess the effects of the p53-Rb pathway on tubular cell senescence. (techscience.com)

Activates1

• Any process that activates or increases the frequency, rate or extent of the activity of any intracellular steroid hormone receptor signaling pathway. (mcw.edu)

Intrinsic1

• Intrinsic factors include chronically activated proliferative, invasive, and antiapoptotic signaling pathways. (springer.com)

Increases1

• DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)

Negatively1

• Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. (kegg.jp)

PI3K1

• Among these pathways, PI3K/Akt signalling cascade plays a very important role in HPV-induced carcinogenesis. (genome.jp)

Cellular3

• The Response To Uv Pathway has been researched in relation to Dna Repair, Cell Cycle, Cell Death, Dna Replication, Cellular Response To Uv. (novusbio.com)
• A series of cellular pathophysiological mechanisms involved in AS (e.g., differentiation, proliferation, and signalling pathways) are under the control of miRNAs. (hindawi.com)
• The mechanisms by which copy number change occurs and the cellular pathways that suppress copy number change are largely unknown. (uri.edu)

Accumulation1

• Finally, CGS21680 reduces cholesterol accumulation (Filipin III staining), which is the main criterion currently used for identification of a compound or pathway that would be beneficial for NPC disease, and such an effect is prevented by the Ca 2+ chelator BAPTA-AM. Our findings strongly support the hypothesis that A 2A R agonists may represent a therapeutic option for NPC1 and provide insights on their mechanisms of action. (jneurosci.org)

Gene2

• The 3′UTR-binding sequence site of miR-128-5p on the p21 gene was predicted and assessed by luciferase assays. (hindawi.com)
• Our research showed that the migration, phenotypic transformation, and proliferation of ox-LDL-induced VSMCs were repressed by AA through inhibiting miR-128-5p by targeting the p21 gene, which may provide an effective option for the treatment of atherosclerosis. (hindawi.com)

Molecular2

• Further studies are required to clarify the intra cel lular molecular pathways affecting NDRG1 function in human prostate cancer. (scirp.org)
• Intriguingly, many of these mechanisms utilize the same molecular pathways that are altered through calorie and/or carbohydrate restriction. (springer.com)

Antigen1

• Here, we review some of the recent advances and studies that highlight the roles of these changes as well as antigen presentation and stress response pathways in beta cells in the onset and propagation of the autoimmune process in type 1 diabetes. (springer.com)

Cell cycle1

• Loss of sensitivity to p21 cell cycle control may be associated with prostatic cancer behavior. (scirp.org)

Neoplasms1

• Disease and disorder research has been conducted in relation to the Response To Uv Pathway and Neoplasms, Malignant Neoplasms, Skin Neoplasms, Malignant Neoplasm Of Skin, Carcinogenesis. (novusbio.com)

Inhibits1

• Wu M, Sun Y, Xu F, Liang Y, Liu H, Yi Y. Annexin A2 Silencing Inhibits Proliferation and Epithelial-to-mesenchymal Transition through p53-Dependent Pathway in NSCLCs. (jcancer.org)

Insulin1

• This complication is a result of multiple pathogenic processes caused by hyperglycemia and the deregulation of insulin signalling pathways, which in turn causes neuro-retinal dysfunction and retinal microvascular degeneration ( 2 , 3 ). (spandidos-publications.com)

Inflammatory1

• It has been reported that Alisma orientale has a protective effect on acute lung injury through an anti-inflammatory effect by repressing the NF-kappa B pathway [ 20 ]. (hindawi.com)

Intracellular1

• This pathway plays a prominent role in inter- and intracellular communication and subversion can lead to cancer, fibrosis vascular disorders, and immune diseases. (lu.se)

Human2

• These results show that human CD34(+) cells are sensitive targets for 1,4-BQ toxicity that use the p53 DNA damage response pathway in response to genotoxic stress. (rti.org)
• 2. Find values for the kinetic parameters from experimental b pathway have been detected in several human diseases, estimates or by fitting the model to experimental kinetic most notably in many forms of cancer, and in fibrotic diseases data. (lu.se)

Response4

• The study of the Response To Uv Pathway has been mentioned in research publications which can be found using our bioinformatics tool below. (novusbio.com)
• The Response To Uv Pathway complements our catalog of research reagents including antibodies and ELISA kits against TP53, JUN, CDKN1A, MAPK8, PCNA. (novusbio.com)
• We have 3206 products for the study of the Response To Uv Pathway that can be applied to Chromatin Immunoprecipitation, Chromatin Immunoprecipitation (ChIP), Flow Cytometry, Immunocytochemistry/Immunofluorescence, Immunohistochemistry, Western Blot from our catalog of antibodies and ELISA kits. (novusbio.com)
• The Fanconi anemia pathway is required for the DNA replication stress response and the regulation of common fragile site stability. (uri.edu)

Role1

• We have recently uncovered an important role for the FA-BRCA pathway in the suppression of de novo copy number change, and are using multiple approaches to further characterize this function. (uri.edu)

Cells1

• ACT‑3 significantly increased the pERK1/2 and p21 in MCF‑7 cells. (iasp-pain.org)