• Primarily, p53 protects the cell from malignant transformation through cell cycle arrest and apoptosis. (uib.no)
  • Loss of ARF results in diminished p53-function and impaired senescence, but does not impact apoptosis. (figshare.com)
  • In this study, we examined CEPA-induced gene expression in DLD-1 colorectal adenocarcinoma human cells carrying a mutant p53, in order to understand the details of CEPA-induced apoptosis via lipid peroxidation. (elsevierpure.com)
  • CEPA treatment caused up-regulation of expression of genes induced by p53 and activation of the mitochondrial apoptosis pathway via Bax and the death pathway via TRAIL, leading to apoptosis of DLD-1 cells. (elsevierpure.com)
  • This is the first such gene expression analysis of the effects of CEPA, and our results confirm that CEPA induces lipid peroxidation, activates mutant p53, and causes p53-dependent apoptosis in DLD-1 cells. (elsevierpure.com)
  • NQ induced apoptosis in HepG2 cells by activating p53-ROS crosstalk and induces epigenetic modifications leading to inhibited proliferation and cell cycle arrest. (molcells.org)
  • The requirement of p53 for FOXO3a-induced apoptosis implied that there might be a functional conversation between these two transcription factors. (forgetmenotinitiative.org)
  • Endogenous p53 provides been proven to induce apoptosis in the current presence of a nuclear import inhibitor, recommending cytosolic p53 may retain some proapoptotic activity even though its nuclear activity is certainly impaired (17). (forgetmenotinitiative.org)
  • To regulate how p53 is certainly governed by FOXO3a during FOXO3a-triggered apoptosis, we examined WT p53 subcellular localization in response to TM-ER activation initial. (forgetmenotinitiative.org)
  • SPIN1 ablation activates p53, suppresses cell growth, reduces clonogenic ability, and induces apoptosis of human cancer cells. (elifesciences.org)
  • Gradual reduction in rRNA transcription triggers p53 acetylation and apoptosis via MYBBP1A. (nih.gov)
  • Expression of latency-associated nuclear antigen (LANA) causes binding of p53 and suppression of apoptosis. (aad.org)
  • Effect of cadmium on P53 and mitogen-activated protein kinases in a murine macrophage cell line: relation to apoptosis. (cdc.gov)
  • Present study was designed to determine the impact of cadmium on cell proliferation, cell cycle and apoptosis, and to investigate the possible involvement of p53 and MAPKs signaling pathways in J774A.1 murine macrophages. (cdc.gov)
  • Results suggested that p53 is not involved in Cd-induced cell cycle arrest and apoptosis in J774A.1 cells. (cdc.gov)
  • If the damage is not repaired on time, the activation of p53 results in programmed cell death known as apoptosis. (scienceblog.com)
  • UV-B-induced DNA damage can trigger cell signaling pathways to activate defense systems, leading to DNA repair and/or apoptosis ( 6 ). (spandidos-publications.com)
  • When DNA becomes damaged, p53 helps determine whether the DNA will be repaired or the cell will self-destruct ( undergo apoptosis ). (medlineplus.gov)
  • p53 is a transcription factor that participates in cell cycle checkpoint processes and apoptosis. (lu.se)
  • This leads to activation of p53 and the p53 pathway in cancer cells with wild type p53, subsequently inhibiting tumour growth. (uib.no)
  • By activating Mdm2, the signal transduction pathway will trigger the anti-apoptotic downstream effects of Mdm2. (wikipedia.org)
  • 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)
  • Mice lacking the gene for Dmp1 commonly develop lung tumors, and Dmp1 has been identified as a regulator of the Arf-p53 pathway in vitro. (eurekalert.org)
  • Further, in K-rasLA mice, lung carcinomas were associated with either p53 mutations or deletion of Dmp1 to inactivate the Arf-p53 pathway. (eurekalert.org)
  • We have demonstrated that the hDMP1 gene is hemizygously deleted in a significant percentage of mouse and human non-small-cell lung carcinomas, especially those which retained the intact Arf-p53 pathway," explains Dr. Inoue. (eurekalert.org)
  • According to Bishop and Lynch: "After infecting endothelial cells, HHV-8 activates the mTOR pathway, alters the cells to have mesenchymal differentiation, and promotes aberrant angiogenesis. (aad.org)
  • The p53 tumour suppressor protein is a key component of one such stress-response pathway, and virtually all cancers loose functionality of the p53-stress response pathway. (southampton.ac.uk)
  • In the late 1990s work from a number of groups, including Blaydes et al , demonstrated that HDM2 could be targeted in cancer cells to re-activate the p53 stress-response pathway. (southampton.ac.uk)
  • Identifying this role for tumor-suppressing p53 provides both a potential biomarker for response to important new cancer immunotherapy drugs and a possible new therapeutic pathway for treatment," said James Welsh, M.D. , associate professor of Radiation Oncology at MD Anderson and senior author. (mdanderson.org)
  • The present study evaluated the protective effects of PF on UV‑induced skin damage in vitro, and demonstrated that the effects were mediated via the ROS‑p38‑p53 pathway. (spandidos-publications.com)
  • Treatment with PF markedly reduced the production of ROS, and inhibited the activation of p38 and p53 in human keratinocytes, thus suggesting that the ROS‑p38‑p53 pathway has a role in UV‑B‑induced skin damage. (spandidos-publications.com)
  • Notably, these effects were shown to be mediated, at least in part, via inhibition of the ROS-p38-p53 pathway. (spandidos-publications.com)
  • 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)
  • In the intrinsic pathway, several adverse factors act upon mitochondria to cause loss of the mitochondrial membrane potential, resulting in leakage into the cytosol of cytochrome C (Cyto C), which together with apoptotic protease activating factor 1 forms the apoptosome that activates caspase-9. (cdc.gov)
  • Akbari MR, Malekzadeh R, Nasrollahzadeh D, activates EGFR pathway signaling in the lung. (who.int)
  • TBC1D15 activated three novel oncogenic pathways to promote self-renewal, p53 loss, and Nanog transcription in TICs. (nature.com)
  • In this study, we hypothesized that 5-ASA restrains cell cycle progression by activating checkpoint pathways in colorectal cell lines, which would prevent tumor development and improve genomic stability. (nih.gov)
  • A previous report found that a broader purchase Obatoclax mesylate range of apoptotic stimuli could regulate PUMA expression, including cell death pathways that are mediated indie of p53 transcription activity. (forgetmenotinitiative.org)
  • Genotoxic damage causes robust alterations to pathways associated with B cell activation and increased proliferation, suggesting that genotoxic damage initiates not only the normal B cell maturation processes but also mimics activated B cell response to antigenic agents. (biomedcentral.com)
  • Scientists have identified the transcription factor DMP1 as a pivotal tumor suppressor for both human and mouse lung cancers, especially in carcinomas that exhibit intact Arf-p53 pathways. (eurekalert.org)
  • Transcriptional responses to pathways: roles in the causes and treatment of cancer Intra-cellular stress-response pathways are activated in response to potentially deleterious conditions in the cell's environment. (southampton.ac.uk)
  • Many current and prospective treatments for cancer work by either inhibiting, or re-activating stress response pathways.Our work focuses on the role of regulators of gene transcription in the response of cancer cells to stress. (southampton.ac.uk)
  • A particular interest of our work has been how HDM2 and HDMX protein synthesis is controlled in response to cell-signalling pathways in different cell types, and how this affects p53 function in these cells. (southampton.ac.uk)
  • Aberrant expression and glycosylation of mucins contribute to tumour survival and proliferation in many cancers, which in turn activates numerous signalling pathways such as NF-kB, ERα, HIF, MAPK, p53, c-Src, Wnt and JAK-STAT, etc. (amrita.edu)
  • These previous results indicated that the ROS-p38-p53 pathways are involved in UV-induced cell damage. (spandidos-publications.com)
  • When these proteins are turned on (activated) by binding to other molecules, signaling pathways are triggered within cells that promote cell proliferation. (medlineplus.gov)
  • Kdm6a Deficiency Activates Inflammatory Pathways, Promotes M2 Macrophage Polarization, and Causes Bladder Cancer in Cooperation with p53 Dysfunction. (bvsalud.org)
  • While mutations in p53 occur in less than 10% of acute myeloid leukaemia (AML), over-expression of the main negative regulator of p53, MDM2, is frequently observed, representing a mechanism of p53 silencing. (uib.no)
  • Some Example Projects: Regulation of HDM2 and HDMX proteins The HDM2 oncoprotein is the major negative regulator of p53 function in the cell. (southampton.ac.uk)
  • In addition, activation of the mutant p53 was also induced by CEPA, and these effects showed lipid-peroxidation dependency. (elsevierpure.com)
  • For instance, serum deprivation could induce mRNA level in tumor cells bearing mutant p53, however the relevant downstream transcription elements involved stay unknown (10). (forgetmenotinitiative.org)
  • The antibody should recognize human wild-type and mutant p53. (abcam.com)
  • Molecular, biochemical, and cell biological studies showed that TP53 loss increased the expression of Golgi reassembly and stacking protein 55 kDa (G55), a Golgi stacking protein that maintains Golgi organelle integrity and is part of a GOLGIN45 (G45)-myosin IIA-containing protein complex that activates secretory vesicle biogenesis in the Golgi. (jci.org)
  • p53 is a tumour suppressor protein involved in maintenance of genomic stability of the cell. (uib.no)
  • Cell-fate-determinant molecule NUMB-interacting protein (TBC1D15) is overexpressed and contributes to p53 degradation in TICs. (nature.com)
  • The p53 interacting partner protein NUMB (homology of numb protein) preserves this intrinsic cellular asymmetry by preventing ubiquitin-mediated proteolysis of p53 catalyzed by the MDM2 E3 ubiquitin ligase 11 . (nature.com)
  • To explore this possibility, we decided p53 protein levels as well as p53 transcriptional activity in WT TM-ER and WT TMDB-ER cells. (forgetmenotinitiative.org)
  • Upon addition of 4-OHT, p53 protein was markedly increased in TM-ER cells but not in TMDB-ER cells (Fig. 1and and mRNA had been evaluated by quantitative real-time PCR and normalized to regulate mRNA. (forgetmenotinitiative.org)
  • They further link to the activation of protein kinase C- (PKC-) induced generation of reactive oxygen species (ROS) [ 6 , 7 ], which further mediates the activation of downstream transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF- κ B). Thus, the main treatments of DN refer to modulate glycemic and blood pressure through insulin and RAS inhibitors. (hindawi.com)
  • We have a long-standing interest in the p53 protein, a stress-activated transcriptional activator. (southampton.ac.uk)
  • We have shown that CtBPs also interact with HDM2 protein, and can consequently regulate p53 function (Mirnezami et al, 2003). (southampton.ac.uk)
  • Welsh and colleagues found that p53 also blocks a protein called PDL1 that tumor cells can wield to halt immune attack. (mdanderson.org)
  • Cycloheximide, an inhibitor of protein synthesis, did not alter Cd-induced cytotoxicity indicating that J774A.1 cell death by Cd is independent of de novo protein synthesis including p53. (cdc.gov)
  • Formed by an international research team, the study served to discover that this protein played an unexpected physiological role: it also becomes activated during the formation process of ova and spermatozoids. (scienceblog.com)
  • The protein becomes activated in response to specific signals such as breaks in DNA. (scienceblog.com)
  • The TP53 gene provides instructions for making a protein, called p53, that is located in the nucleus of cells throughout the body, where it attaches (binds) directly to DNA. (medlineplus.gov)
  • TP53 gene mutations result in the production of an altered p53 protein that cannot bind to DNA. (medlineplus.gov)
  • The protein product of the murine double minute gene 2 (mdm-2) plays a central role in the regulation of p53. (lu.se)
  • PUMA could action through getting together with antiapoptotic Bcl-2 associates, which liberates various other BH3 proteins that may activate Bax or Bak (11C15). (forgetmenotinitiative.org)
  • Role of CtBP transcriptional repressors in cancer cell proliferation and survival In common with p53, CtBP1 and CtBP2 proteins were discovered through their physical association with a viral oncoprotein. (southampton.ac.uk)
  • Among these cell-signaling proteins, activation of p53 is important in cells with UV radiation-induced DNA damage ( 4 , 7 ). (spandidos-publications.com)
  • The well-documented tumor suppressor p53, referred as 'the guardian of the genome', is activated upon exposure to a myriad of cellular stresses. (elifesciences.org)
  • In keeping with the gel change outcomes, the ChIP assays demonstrated that FOXO3a-TM activation decreased the association of p53 using the endogenous or promoters on Etop treatment (Fig. 2DNA binding activity of p53 is certainly inhibited by FOXO3a-TM, in the current presence of DNA damage alerts also. (forgetmenotinitiative.org)
  • Pretreatment of cells with SB202190, a p38 inhibitor, may inhibit the DNA binding activity of p53 and suppress p53-dependent transcription ( 10 ). (spandidos-publications.com)
  • Given the involvement of p53, compaction hypersensitivity may be widespread among damaged cells and offers an additional route to eliminate unfit cells. (nature.com)
  • DEK functions as a transcriptional repressor by interfering with histone acetyl transferases, regulator for a number of stem cells, and activates gene expression in myeloid cells (Koleva et al. (wikipedia.org)
  • Importantly, we show that elevation of the tumour suppressor p53 is necessary and sufficient for crowding hypersensitivity. (nature.com)
  • p14ARF is a well known tumor suppressor that serves as the safety net when p53 tumor suppressor's functions are inhibited. (wikipedia.org)
  • Dmp1 is a unique tumor suppressor that activates Arf expression and thus induces p53-dependent cell cycle arrest. (eurekalert.org)
  • From an evolutionary point of view it is understandable to think that p53 came into existence without necessarily acting as a tumour suppressor and, therefore, must have had other functions which until now remained unknown. (scienceblog.com)
  • The research describes for the first time the physiological role of p53 in the development of meiosis and suggests that the function of the tumour suppressor gene can be result of an evolution of primitive activities related with the progression of meiosis. (scienceblog.com)
  • With no p14ARF to regulate and inhibit Mdm2, there will be an increased level of suppression of p53. (wikipedia.org)
  • We discovered that FOXO3a could regulate PUMA at transcriptional level indie of p53 (H.Con. (forgetmenotinitiative.org)
  • While it is known that genotoxic agents, such as IR, activate transcriptional programs involved in maintaining the integrity of the genome, we also want to investigate whether or not the genotoxic breaks could affect lymphocyte-specific maturation transcriptional responses similar to those we observed following RAG-induced physiological DSBs. (biomedcentral.com)
  • Specifically, we show that scrib KD cells' compaction causes activation of the Rho-associated kinase (ROCK), which in turn activates p38 leading to further p53 elevation and cell death. (nature.com)
  • Nutlin-3 is a non-genotoxic MDM2 antagonist, which specifically disrupts the MDM2-p53 interaction by binding to the p53 specific site on MDM2. (uib.no)
  • Mdm2 is a proto-oncogene that directly antagonizes p53 to ubiquitination (Figure 1). (wikipedia.org)
  • Mechanistically, SPIN1 sequesters uL18 in the nucleolus, preventing it from interacting with MDM2, and thereby alleviating uL18-mediated inhibition of MDM2 ubiquitin ligase activity toward p53. (elifesciences.org)
  • TP53 loss activated G55-dependent secretion by relieving G55 and myosin IIA from miR-34a-dependent silencing. (jci.org)
  • While loss of wild-type p53 causes fatal damages to the genome, it is not surprising that the TP53 gene is mutated in more than 50% human cancers, and the functions of p53 are often impeded through various mechanisms in the remainder ( Levine and Oren, 2009 ). (elifesciences.org)
  • Treatment with Cd at 20 and 50 microM induced phosphorylation of extracellular signal-regulated kinase (ERK), but did not alter p53 mRNA expression or the activation of p38 MAPK and c-Jun N-terminal MAPK. (cdc.gov)
  • p38 acts as a stress-activated MAPK that is preferentially activated by diverse cellular stressors, including UV-B-induced oxidative stress ( 9 ). (spandidos-publications.com)
  • The p53 gene is damaged, missing or under-expressed in 42% of common cancers and 70% of lung cancers. (mdanderson.org)
  • Mutations that activate the oncogene K-ras or interfere with the tumor suppressors p53 and Arf are common in human NSCLCs. (eurekalert.org)
  • When we examined p53 downstream targets levels in TM-ER cells, all chosen targets were down-regulated upon TM-ER induction detected by RT-PCR and further confirmed by quantitative real-time PCR, except PUMA (data not shown). (forgetmenotinitiative.org)
  • Hypoxia changes the cellular redox state and activates class III histone deacetylase sirtuin1 (SIRT1). (molvis.org)
  • TBC1D15-NOTCH1 interaction activated and stabilized NOTCH1 which upregulated transcription of NANOG essential for TIC expansion. (nature.com)
  • The interaction is specific: p53 activates the micro RNA miR-34a, which in turn directly blocks expression of PDL1," said Cortez. (mdanderson.org)
  • Terphenyl-based helical mimetics that disrupt the p53/HDM2 interaction. (nyu.edu)
  • however, the Cd-modulated p53 and MAPKs signaling mechanisms leading to cellular toxicity on macrophages have not been investigated. (cdc.gov)
  • Through the observation of genetically modified flies to determine the activation of p53, the team led by Dr John Abrams of the University of Texas Southwestern Medical Center and with the participation of Dr Ignasi Roig from the Cytology and Histology Unit of the Department of Cellular Biology, Physiology and Immunology at Universitat Autònoma de Barcelona, discovered that p53 becomes activated during the formation of gametes (spermatozoids and ova). (scienceblog.com)
  • Pretreatment of cells with N-acetyl-L-cysteine (NAC), an agent known to counteract oxidative stress, attenuates the cellular p53 response to UV ( 4 ). (spandidos-publications.com)
  • These two therapeutic compounds both indirectly activate p53, thereby presenting a combinational non-genotoxic p53 activation strategy, in contrast to conventional chemotherapy and bone marrow transplantation. (uib.no)
  • Compaction, via activation of Rho-associated kinase (ROCK) and the stress kinase p38, leads to further p53 elevation, causing cell death. (nature.com)
  • Subcellular Localization Transformation of p53 upon Activation of FOXO3a. (forgetmenotinitiative.org)
  • SPIN1 deficiency increases ribosome-free uL18 and uL5 (human RPL11), which are required for SPIN1 depletion-induced p53 activation. (elifesciences.org)
  • Consistent with this finding, human lung carcinomas exhibited loss of hDMP1 in a mostly exclusive fashion with loss of Arf-p53 activation. (eurekalert.org)
  • In addition, oxidative stress is associated with UV-induced activation of p53 ( 4 ). (spandidos-publications.com)
  • HDACs deacetylate histones and transcription factors such as p53, leading to increased chromatin compaction, representing an additional means for silencing p53 activity. (uib.no)
  • We find that scrib KD cells are hypersensitive to compaction and that this is due to elevation of baseline p53 levels, which is both necessary and sufficient to induce hypersensitivity to crowding and confer a mechanical loser status. (nature.com)
  • Altogether, our findings reveal that the oncogenic property of SPIN1 may be attributed to its negative regulation of uL18, leading to p53 inactivation. (elifesciences.org)
  • Mutually Exclusive Inactivation of DMP1 and ARF/p53 in Lung Cancer. (eurekalert.org)
  • Nutlin-3 and VPA in combination was found to show a synergistic effect in vitro in an AML cell line expressing wild type p53 (MOLM-13). (uib.no)
  • Overall, this work demonstrates that mechanical forces can be responsible for the elimination of cells during cell competition and that p53 levels play a key role both in instructing the mechanical loser status and in the execution of mechanical cell competition. (nature.com)
  • This effect was independent of the hMLH1, hMSH2, and p53 status because it was observed to a similar extent in all cell lines under investigation. (nih.gov)
  • TM-ER steady MEF cell series (Fig. 3in purchase Obatoclax mesylate p53QSA135V cells had been similar with their amounts in p53 lacking MEFs (data not really shown). (forgetmenotinitiative.org)
  • These results suggest genotoxic damage may induce a unique cancer-prone phenotype and processes mimicking activated B cell response to antigenic agents, as well as the normal B cell maturation processes. (biomedcentral.com)
  • It becomes activated specifically during meiosis, the cell division process resulting in gametes. (scienceblog.com)
  • First author Maria Angelica Cortez, Ph.D. , instructor of Experimental Radiation Oncology, identified the mechanism by which p53 blocks expression of PDL1. (mdanderson.org)
  • P53 is in charge of developing this process control mechanism. (scienceblog.com)
  • This in turn results in aPKCζ-mediated NUMB phosphorylation, NUMB dissociation from p53, and p53 degradation (Fig. 1a ) 12 . (nature.com)
  • It has previously been reported that p38 mediates UV-induced phosphorylation of p53. (spandidos-publications.com)
  • VPA is a well-tolerated non-genotoxic HDAC inhibitor inhibiting deacetylation of chromatin and transcription factors such as p53, and has been found to show an anti-leukemic effect in AML patients. (uib.no)
  • We have previously shown that the inflammatory transcription factor nuclear factor of activated T-cells 2 (NFATC1) is overexpressed in FLT3ITD-positive AML, yet its role in the transformation and AML development is unknown. (uni-marburg.de)
  • CRC cells with different genetic backgrounds such as HT29, HCT116, HCT116(p53-/-), HCT116+chr3, and LoVo were treated with 5-ASA for 2-96 hours. (nih.gov)
  • Our data demonstrate that 5-ASA causes cells to reversibly accumulate in S phase and activate an ATR-dependent checkpoint. (nih.gov)
  • Upon addition of 4-OHT, cytosolic p53 deposition was seen in WT TM-ER cells (Fig. 5and appearance amounts had been discovered by quantitative real-time PCR. (forgetmenotinitiative.org)
  • Importantly, Dmp1 overexpression inhibited growth of human lung cancer cells with K-ras mutation and wild-type Arf and p53. (eurekalert.org)
  • Scientists have long known that p53 plays a central role in cancer control by regulating a process that forces abnormal cells to repair themselves and, failing that, to kill themselves. (mdanderson.org)
  • Like a key, PDL1 connects with and activates a checkpoint molecule called PD1 found on the surface of T cells that shuts down those killer white blood cells. (mdanderson.org)
  • AML1, located at the 21q22, normally has the ability to activate transcription of the ARF gene and ETO, located at the 8q22, normally has the ability to repress transcription. (wikipedia.org)
  • While p53 had been linked to other aspects of immune response, the JNCI paper is the first to connect it to immune evasion by tumors and regulation of PDL1. (mdanderson.org)
  • These pilot results suggests the p53 activating strategy as a valuable concept in the treatment of AML, and should indeed be further evaluated. (uib.no)
  • The oncogenic role of TLR4 activated by endotoxin has been confirmed by others in a different liver tumor model 10 . (nature.com)
  • Although p53 did not have a causative role, p53 Ser15 was strongly phosphorylated. (nih.gov)
  • This preclinical research shows an experimental drug currently in phase I clinical trials can replace the immunity-protecting role lost when p53 fails. (mdanderson.org)
  • 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)
  • Our study results demonstrate that hypoxia mimetic cobalt chloride induces SIRT1 and augments HIF-2α, which activates and releases VEGF. (molvis.org)
  • p53 staining status was not associated with response to treatment in either 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)
  • 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)