• p53 is a master gene regulator controlling diverse cellular pathways, by either activating or repressing downstream genes. (bioinf.org)
  • One of the activated genes is an inhibitor of cyclin-dependent kinases. (lsbio.com)
  • Because BRCA mutations are observed in fewer than 10% of cancer patients (cBioPortal: 6.7%) 11 , 12 , 13 the identification of additional genes that share synthetic lethal sensitivity relationships with mutated oncogenes or tumor suppressors would greatly enhance the implementation of tumor cell-specific synthetic lethal sensitivity to improve an anticancer therapeutic response. (nature.com)
  • Early studies of transforming retroviruses led to discovery of oncogenes, while studies of DNA viruses (like AV40) led to discovery of p53 and Rb and tumor suppressor genes. (stackexchange.com)
  • Cellular signaling pathways are networks of genes, proteins, enzymes, cytokines, and other cellular species that "communicate" in order to govern the basic functions of cells. (american.edu)
  • Importantly, in the cohort studied, Ser312 mutation predisposes mice to develop thymic lymphomas and liver tumors, partly due to p53Ser312Ala's inability to fully induce a set of p53 target genes including p21 and cyclin G1. (ox.ac.uk)
  • Currently intense focus centers on understanding how p53 chooses which of its multiple target genes to activate or repress in response to a given stress. (opioid-receptors.com)
  • A potential source enabling the diverse functions of p53 lies within the core promoter regions of its target genes [5]. (opioid-receptors.com)
  • By comparing the p53 protein level and its ability to transactivate target genes Waf1/Cip1 and mdm2 in both T22 and NIH3T3 cells irradiated with u.v., a discordance between the p53 protein level and its transcriptional activity was observed. (ox.ac.uk)
  • The observed lack of correlation between the elevated p53 and beta-galactosidase and expression in u.v. irradiated cells strongly indicates that the ability of p53 to transactivate its target genes is not simply correlated to its protein level. (ox.ac.uk)
  • A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human CHROMOSOME 17 at locus 17q21. (lookformedical.com)
  • A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 13 at locus 13q12.3. (lookformedical.com)
  • This week in Nature Genetics , two studies report recurrent mutations in splicing-related genes in blood tumors. (massgenomics.org)
  • Several genetic alterations have been described in SCCHN, including mutations in the p53 tumor suppressor gene and mutations in genes that encode cell cycle proteins such as p16 and cyclin D1. (oncotarget.com)
  • In addition, these alterations affect 3 principal categories of genes, as follows: proto-oncogenes, tumor suppressor genes, and DNA repair genes. (medscape.com)
  • This article briefly discusses tumor suppressor genes and then focuses on the role of proto-oncogenes in childhood cancer. (medscape.com)
  • Inactivation of tumor suppressor genes, whose products normally provide negative control of cell proliferation, contributes to malignant transformation in various cell types. (medscape.com)
  • Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)
  • Another important class of tumor suppressor genes involved in cell cycle control and in the generation of human cancers is the cyclin-dependent kinase (CDK) inhibitors. (medscape.com)
  • Although carcinogenic roles for the INK4B, INK4C, INK4D, CIP1, KIP1, and KIP2 genes appear to be limited, INK4A is among the most commonly mutated genes in human tumors. (medscape.com)
  • Pansensitive and panresistant genes to 21 NCCN-recommended drugs with concordant mRNA and protein expression were identified. (cdc.gov)
  • Conclusions These findings ascertained an conversation between p53, c-myc, p21, p27, Bcl-2, PI3K/Akt pathway, and CF-induced apoptosis in MSTO-211H and HCT-116 cells, suggesting that CF acts as an important regulator of cell growth in human malignancy cell lines. (bioinf.org)
  • Our simulations show that, if HMGB1 is overexpressed, then the oncoproteins CyclinD/E, which regulate cell proliferation, are overexpressed, while tumor suppressor proteins that regulate cell apoptosis (programmed cell death), such as p53, are repressed. (biomedcentral.com)
  • The HMGB1 signal transduction can influence the cell's fate by two important processes - apoptosis and cell proliferation - which are regulated respectively by the proteins p53 and CyclinE, acting in two different signaling pathways. (biomedcentral.com)
  • The protein p53 is one of the most important tumor suppressor proteins: its activation can lead to cell cycle arrest, DNA repair, or apoptosis. (biomedcentral.com)
  • In this paper, we ask the following questions: How do these proteins and their mutations change the cell's fate - apoptosis or survival - when HMGB1 signal transduction is activated? (biomedcentral.com)
  • Everolimus-mediated apoptosis was also associated with an upregulation of p53 upregulated modulator of apoptosis (PUMA-α) proteins, an increase in Bax proteins and downregulation of Bcl-x(L) proteins in all tested HTLV-I-positive and -negative malignant cell lines. (edu.lb)
  • The present study assessed, by immunohistochemistry, the microvessel density in the synovium of these arthritides and in normal controls, in relation to the expression of the angiogenic factors vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) and the apoptosis-related proteins bcl-2 and p53. (ox.ac.uk)
  • Treating SCCHN cell lines with a pan-Aurora kinase inhibitor resulted in defective cytokinesis, polyploidy and apoptosis, which was effective irrespective of the EGFR status. (oncotarget.com)
  • Our results demonstrate that combined targeting of EGFR and Aurora kinases represents a therapeutic means to activate cell cycle checkpoints and apoptosis in SCCHN. (oncotarget.com)
  • Interacting with various cellular proteins, E6 and E7 influence fundamental cellular functions like cell cycle regulation, telomere maintenance, susceptibility to apoptosis, intercellular adhesion and regulation of immune responses. (asspub.ro)
  • The p53 protein is an important tumor suppressor that is essential for regulating cell division, senescence, and self-destruction (apoptosis). (medlineplus.gov)
  • p53 is a transcription factor that participates in cell cycle checkpoint processes and apoptosis. (lu.se)
  • The various markers that enable assessment of the progression of preneoplastic lesions to spindle cell carcinoma include the p16 protein, which halts the cell cycle and induces apoptosis by pRb-mediated phosphorylation of cyclin-dependent kinase 4 (CDK4). (bvsalud.org)
  • On Western blots, the full-length ATM protein was detected in eight of 18 AT cases, albeit at 1-32% of the normal levels, whereas a truncated ATM protein was detected in a single case, despite the prevalence among cases of truncation mutations. (nih.gov)
  • Altogether, our study shows that AT and A(-T) cases bearing truncation mutations of the ATM gene can produce modest amounts of full-length (and only rarely truncated) ATM protein. (nih.gov)
  • p53 mutations in human cancers. (lsbio.com)
  • Because most tumors are deficient in one or more aspects of the function of the p53 tumor suppressor, either as a consequence of mutations within p53, or impairment of upstream and downstream modulators of p53 activity 19 , targeting MK2 has the potential to selectively enhance tumor cell killing without increasing the genotoxic effects of chemotherapy on normal p53-wild type tissues. (nature.com)
  • By using a direct in vivo shRNA screen, we show that liver cancer cells that have mutations in the gene encoding the tumor suppressor protein p53 (Trp53 in mice and TP53 in humans) and that are driven by the oncoprotein NRAS become addicted to MYC stabilization via a mechanism mediated by aurora kinase A (AURKA). (scite.ai)
  • Mutations of p53 occur at a frequency of 50% or higher in many different cancer types [ 13 ]. (biomedcentral.com)
  • Physique 1 Structural representations of the kinase inhibitors Hyericin Rottlerin and SP600125 The p53 tumor suppressor protein promotes longevity by reducing somatic mutations or the survival and proliferation of mutant cells [4]. (opioid-receptors.com)
  • Most of these mutations lead to production of little or no functional p16(INK4A) protein. (medlineplus.gov)
  • The CDKN2A gene mutations found in melanoma result in a nonfunctional p16(INK4A) protein. (medlineplus.gov)
  • Together, the germline and somatic mutations impair the function of proteins that regulate division and senescence, leading to uncontrolled cell growth and the formation of a melanoma. (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)
  • Expression of p63 is almost exclusively restricted to epithelial cells, mutations in this gene are infrequent, and its expression is increased in a variety of solid tumors, particularly those of the head and neck area 12,13 . (bvsalud.org)
  • The radiation-induced phosphorylation of p53 protein at serine 15, largely mediated by ATM kinase, was defective in AT, A(-T) and in 2/4 heterozygous carriers, while the G1 cell cycle checkpoint was disrupted in all AT and A(-T) cases, and in 3/10 AT heterozygotes. (nih.gov)
  • Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. (reactome.org)
  • However, it is not known in which cell types CK2-mediated phosphorylation of p53 occurs. (dundee.ac.uk)
  • Dual-immunofluorescence also revealed that Ser392 and Ser15 phosphorylation of p53 also occur in the same basal cells, although often within distinct regions of the nucleus. (dundee.ac.uk)
  • In response to DNA double strand breaks, serine at position 15 of the TP53 (p53) tumor suppressor protein is rapidly phosphorylated by the ATM kinase. (reactome.org)
  • For example, the TP53 gene, located on chromosome 17, encodes a 53-kd nuclear protein that functions as a cell cycle checkpoint. (medscape.com)
  • [ 2 ] Targeted disruption of TP53 in the mouse leads to the development of various tumors (see image below). (medscape.com)
  • The p19ARF protein, which is encoded by the same locus as p16, also leads to cell cycle arrest by inhibiting the ability of MDM2 to inactivate TP53. (medscape.com)
  • Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. (lookformedical.com)
  • Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. (lookformedical.com)
  • Knocking down p53 and ERalpha by small interfering RNA elicits opposite effects on p53-target gene expression and cell cycle progression. (nih.gov)
  • In addition to its role in controlling cell cycle progression, the tumor suppressor protein p53 can also affect other cellular functions such as cell migration. (rupress.org)
  • During the progression of colitis, genetic alterations associated with mucosal permeability [ e.g. those in extracellular matrix protein 1 ( ECM1 ), cadherin 1 ( CDH1 ), and hepatocyte nuclear factor 4 alpha ( HNF4A )] have been observed and considered to confer the risk of severe UC ( 11 , 12 ). (iiarjournals.org)
  • Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. (lookformedical.com)
  • Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm. (lookformedical.com)
  • The CDK4-cyclinD complex normally phosphorylates the retinoblastoma protein (Rb protein), leading to release of the E2F transcription factor and cell cycle progression. (medscape.com)
  • 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)
  • Conclusion: p63, p16, MIB, Cal A, Cys A are markedly expressed and p16 is strongly suppressed in oral cavity tumors, which suggests that the latter protein may play a role in negative regulation of cell cycle progression. (bvsalud.org)
  • Recently Cdk5 has emerged as an essential kinase in sensory pathways. (wikipedia.org)
  • The Tax protein has pleiotropic effects on host-cell gene expression and activates several pathways such as the cyclic AMP responsive binding protein (CREB), the nuclear factor kappa-B (NF-κB), the cyclin-dependant kinases (CDKs), and the Akt pathways. (nih.gov)
  • The Tax protein has pleiotropic effects on host-cell gene expression and activates several pathways such as the cyclic AMP responsive binding protein (CREB), the nuclear factor kappa-B, the cyclin-dependant kinases (CDKs), and the Akt pathways. (nih.gov)
  • The cell cycle is strictly regulated and controlled by a complex network of signaling pathways [ 1 ], comprised of hundreds of proteins. (biomedcentral.com)
  • Moreover, a number of extracellular proteins can bind to their receptors and activate signaling pathways that promote the proliferation of cancer cells. (biomedcentral.com)
  • Many studies have found evidence of crosstalk between the two signaling pathways involving p53 and CyclinE [ 15 ]. (biomedcentral.com)
  • These data identify a physiological model with which to identify signaling pathways that mediate cross-talk between p63alphaDeltaN and activating p53 kinase pathways after DNA damage in basal cell populations. (dundee.ac.uk)
  • In the present review, the role of Jak/STAT proteins and their regulators will be discussed in connection with osteoclastogenesis, since growing evidence indicates that a number of cytokines and growth factors utilizing Jak/STAT signaling pathways affect osteoclastogenesis. (koreascience.kr)
  • It encodes a large nuclear protein that is a component of DNA repair pathways. (lookformedical.com)
  • The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (lookformedical.com)
  • It encodes a large, nuclear protein that is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (lookformedical.com)
  • Cdk5 is a proline-directed serine/threonine kinase, which was first identified as a CDK family member due to its similar structure to CDC2/CDK1 in humans, a protein that plays a crucial role in the regulation of the cell cycle. (wikipedia.org)
  • As such, p53 has 123653-11-2 manufacture been described as the guardian of the genome. (bioinf.org)
  • p53, guardian of the genome. (lsbio.com)
  • Furthermore, co-treatment of KFr13Tx cells with MET inhibitors sensitized the tumor cells to PTX both in vitro and in vivo . (nature.com)
  • The concept has now been extended to embrace synthetic lethal drug sensitivity, such as that observed with PARP inhibitors in combination with DNA-damaging chemotherapy in a variety of BRCA defective tumors 10 . (nature.com)
  • Therefore, compared to normal p53-proficient cells, p53-defective cells are more reliant on MK2 activity, which drives an alternative cell cycle checkpoint pathway that stabilizes the CKI inhibitors p27 Kip1 and Gadd45α in order to maintain G 1 /S and G 2 /M arrest after certain types of DNA damage 16 , 18 . (nature.com)
  • Figure1) 1 are kinase inhibitors that impair transcription initiation by targeting components of the Pol II pre-initiation complex. (opioid-receptors.com)
  • analyzed the impact of multiple kinase inhibitors on RNA transcriptional activity along three p53 target gene core regulatory elements using transcription and electrophoretic mobility shift (EMSA) assays. (opioid-receptors.com)
  • PubMed] 3 Morachis J Huang R Emerson B. Id of Kinase Inhibitors the mark Transcription Initiation by RNA Polymerase II. (opioid-receptors.com)
  • The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)
  • The levels of p53 mRNA are comparatively reduced in a subset of cancer specimens, which highly present MCT-1 mRNA. (tmu.edu.tw)
  • In children and adolescents, salivary gland tumors make up 0.5% of all malignancies. (medscape.com)
  • Almost half of all submandibular gland neoplasms and most sublingual and minor salivary gland tumors are malignant. (medscape.com)
  • Successful diagnosis and treatment of patients with salivary gland tumors require a thorough understanding of tumor etiology, biologic behavior of each tumor type, and salivary gland anatomy. (medscape.com)
  • An estimated 700 deaths (0.4 per 100,000 for males and 0.2 per 100,000 for females) related to salivary gland tumors occur annually. (medscape.com)
  • Cdk5 is abundant and mainly expressed in neurons, where it phosphorylates protein polymers with a high molecular weight called neurofilaments, and microtubule-associated protein tau, which are abundant in the CNS (Central Nervous System). (wikipedia.org)
  • ATM associates with and phosphorylates p53: mapping the region of interaction. (reactome.org)
  • Using human skin as a model to determine whether there is cell-selectivity in modulating p53 phosphorylation, we have found a selective induction of p53 phosphorylation at the CK2-site in the basal cells of UV irradiated human skin. (dundee.ac.uk)
  • In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (lookformedical.com)
  • HPV E6 and E7 oncoproteins are the critical molecules in the process of malignant tumour formation. (asspub.ro)
  • It turned out that old cells, on the one hand, act as tumor suppressors (since they irreversibly stop dividing themselves and reduce the risk of transformation of surrounding cells), and on the other hand, the specific metabolism of old cells can cause inflammation and degeneration of neighboring precancerous cells into malignant ones. (vechnayamolodost.ru)
  • But at the same time, renewing tissues are subject to hyperproliferation, which leads to the formation of tumors, including malignant ones. (vechnayamolodost.ru)
  • [ 4 , 5 ] ) Benign neoplasms occur more frequently in women than in men, but malignant tumors are distributed equally between the sexes. (medscape.com)
  • In such a circumstance, the Ras-mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-mitogen-activated protein kinase signaling activity and the expression of metastatic molecules are amplified. (tmu.edu.tw)
  • VEGF is crucial in the process of tumor-induced angiogenesis, and recent experiments strongly suggest that the molecule is most potent when bound to the extracellular matrix (ECM). (proteasomesignaling.com)
  • We characterized the ATM protein expression in immortalized cells from AT and AT-variant patients, and heterozygotes and correlated it with two ATM-dependent radiation responses, G1 checkpoint arrest and p53-Ser 15 phosphorylation. (nih.gov)
  • Estrogen receptor-alpha (ERalpha) promotes proliferation of breast cancer cells, whereas tumor suppressor protein p53 impedes proliferation of cells with genomic damage. (nih.gov)
  • Ionizing radiation together with ERalpha knock down results in additive effect on transcription of endogenous p53-target gene p21 (CDKN1) in human breast cancer cells. (nih.gov)
  • Tax-expressing cells also exhibit nuclear morphological aberrancy, frequent multinucleation, aneuploidy, and loss of function of the tumor suppressor protein p53. (nih.gov)
  • Increased manifestation levels of p53, p21, and p27, downregulation of c-myc and Bcl-2, and inhibition of Akt activation were also found in CF-treated MSTO-211 and HCT-116 cells. (bioinf.org)
  • p53 activation is characterized by a drastic increase and its rapid accumulation in stressed cells [11]. (bioinf.org)
  • Cancer cells that are defective in p53 function are deficient in their ability to transcriptionally upregulate the CDK inhibitor p21 after genotoxic stress. (nature.com)
  • Given that p63alphaDeltaN is required for p53 activation after DNA damage, we examined and found a high proportion of cells co-express p63alphaDeltaN and CK2-phosphorylated p53 after UV-irradiation. (dundee.ac.uk)
  • A similar p53-mediated transition is observed in melanoma A375P cancer cells. (rupress.org)
  • Moreover, tumor cells show an increased capacity to migrate. (rupress.org)
  • While primary SCID (severe combined immunodeficiency) cells, that have defective DNA-PK, show normal p53 activation and cell cycle arrest, a transcriptionally inert form of p53 is induced in the SCID cell line SCGR11. (uthscsa.edu)
  • Remarkably, increases in chromosome copy number, multinucleation, and cytokinesis failure are also promoted while MCT-1 is induced in p53-deficient cells. (tmu.edu.tw)
  • Given a p53-silencing background, MCT-1 malignantly transforms normal breast epithelial cells that are satisfactory for stimulating cell migration/ adhesion and tumorigenesis. (tmu.edu.tw)
  • Detailed analyses of MCT-1 oncogenicity in H1299 p53-null lung cancer cells have shown that ectopically expressed MCT-1 advances xenograft tumorigenicity and angiogenesis, which cannot be completely suppressed by induction of p53. (tmu.edu.tw)
  • We examined the effects of new formula of freezing solution containing 7.5% dimethylsulfoxide (DMSO) (v/v %) and 2.5% polyethylene glycol (PEG) (w/v %) on cell survival and recovery of hES cells after cryopreservation, and further investigated the role of the combination of Rho-associated kinase (ROCK) inhibitor and p53 inhibitor on cell recovery during the subsequent culture. (ox.ac.uk)
  • Matrix assisted laser desorption ionization (MALDI) mass spectrometry is commonly used to analyze biological molecules such as proteins, peptides and lipids from cells or tissue. (koreascience.kr)
  • The role of this protein in chondrocytes is not well understood, although its increase in osteoarthritic cells has been reported. (biomedcentral.com)
  • Among the proteins that were significantly altered in OA chondrocytes, we identified the β subunit of the chaperone Hsp90 as increased in diseased cells. (biomedcentral.com)
  • However, little increase in Waf1/Cip1 and mdm2 expression was observed in T22 and NIH3T3 cells 8 or 9 h after exposure to 50 J/m2 of u.v., although the p53 protein level accumulated to its highest level under these conditions. (ox.ac.uk)
  • Interestingly, a significant increase in Waf1/Cip1 expression was seen 24 h after irradiation in NIH3T3 cells, indicating that the inhibition of p53 transcriptional activity is reversible. (ox.ac.uk)
  • Using double immunofluorescence staining, the coexpression of p53 and beta-galactosidase from the reporter plasmid in the same cells was investigated. (ox.ac.uk)
  • Mutant allele frequencies were at 40-50% , suggesting that the mutation was present in most or all tumor cells. (massgenomics.org)
  • These changes can be inherited and are, therefore, found in every cell, but more often, they are somatically acquired and restricted to tumor cells. (medscape.com)
  • Both function as tumor suppressors, which means they keep cells from growing and dividing too rapidly or in an uncontrolled way. (medlineplus.gov)
  • Both proteins are also involved in stopping cell division in older cells (senescence). (medlineplus.gov)
  • The p14(ARF) and p53 proteins are often made in cells that are unable to undergo cell division. (medlineplus.gov)
  • 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)
  • Without one of these tumor suppressors, cells can grow and divide unchecked, leading to the development of cancer. (medlineplus.gov)
  • This theory holds that tumors arise from 1 of 2 undifferentiated stem cells: the excretory duct reserve cell or the intercalated duct reserve cell. (medscape.com)
  • GEP analyses were performed on highly purified, flow-cytometry sorted tumor-cells from eight subgroups of BCLs. (lu.se)
  • This enabled identification of TFs that can be uniquely associated to the tumor cells of chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), hairy cell leukemia (HCL), and mantle cell lymphoma (MCL). (lu.se)
  • The primary barriers for invading respiratory pathogens are the respiratory tract epithelial cells and antimicrobial proteins generated by these cells. (cdc.gov)
  • Cystatin A (Cys A), a cysteine protease inhibitor, is a precursor of proteins involves in keratinocyte keratinization, and is expressed during the late phase of differentiation of these cells. (bvsalud.org)
  • A diverse range of physiological stimuli induce Akt kinase activity, including many trophic factors which promote survival, at least in part, through Akt activation via the phosphatidylinositide 3-OH kinase 123653-11-2 manufacture (PI3K) signaling cascade. (bioinf.org)
  • Inactivation of p53 Is Sufficient to Induce Development of Pulmonary Hypertension in Rats. (lsbio.com)
  • p73, a member of the p53 family of tumour-suppressor proteins, can also induce apop. (shengsci.com)
  • Although researchers have learned much from the study of this diverse group of tumors over the years, the diagnosis and treatment of salivary gland neoplasms remain complex and challenging problems for the head and neck surgeon. (medscape.com)
  • Salivary gland neoplasms make up 6% of all head and neck tumors. (medscape.com)
  • The most common tumor of the parotid gland is the pleomorphic adenoma , which represents about 60% of all parotid neoplasms, as seen in the table below. (medscape.com)
  • Moreover, the anti-tumor effect of AKI603 was proved in the BALB/c nude mice KBM5-T315I xenograft model. (scite.ai)
  • Genetic studies in mice have shown that mutation of the CK2 phospho-acceptor site in p53 increases UV-induced skin cancer formation,(11) highlighting an unexpected role for p53 phosphorylation in mediating p53-dependent tumor suppression. (dundee.ac.uk)
  • In order to unambiguously define the role of the DNA-PK catalytic subunit (DNA-PKcs) in p53 activation, we examined p53 phosphorylation in mouse embryonic fibroblasts (MEFs) from DNA-PKcs-null mice. (uthscsa.edu)
  • In agreement with the notion that Ser312 mutation weakens p53 function, Ser312Ala mice are also more susceptible to tumorigenesis following a sublethal ionizing radiation dose. (ox.ac.uk)
  • Minocycline is a semi-synthetic second-generation tetracycline known to improve cognition in amyloid precursor protein transgenic mice. (proteasomesignaling.com)
  • Tumors that developed in mice deficient in INK4A were enhanced by the topical application of carcinogens and ultraviolet light. (medscape.com)
  • Cellular iron levels and iron associated proteins are differentially expressed in many cancers, and recently, it was reported that high expression levels of iron importer and low levels of iron exporter were associated with a poor prognosis in breast cancer patients. (american.edu)
  • The p53 tumor-suppressor protein, a key regulator of cellular responses to genotoxic stress, is stabilized and activated after DNA damage. (tau.ac.il)
  • Their studies reveal TAK-700 (Orteronel) that far from being a latent tumor suppressor p53 functions in a temporal manner to regulate promoter activity both before and after cellular stress. (opioid-receptors.com)
  • Ammonia is a product of the metabolism of proteins and other compounds, and it is required for the synthesis of essential cellular compounds. (medscape.com)
  • In order to protect against itself, special cellular mechanisms of tumor suppression have formed in the body. (vechnayamolodost.ru)
  • Good suppression, and it can be configured as a full length or "K" suppressor, but one aspect of the build- subsequently discovered- should be considered before purchase. (dorama.fun)
  • Phosphorylation of Ser312 contributes to tumor suppression by p53 in vivo. (ox.ac.uk)
  • Discrete, stochastic simulations show that p53 and MDM2 oscillations continue even after 10 hours, as observed by experiments. (biomedcentral.com)
  • In this study, we show that p53 deficiency in mouse embryonic fibroblasts cultured in three-dimensional matrices induces a switch from an elongated spindle morphology to a markedly spherical and flexible one associated with highly dynamic membrane blebs. (rupress.org)
  • This is achieved by the ability of p53 to establish markedly different affinities of Poll II on its diverse target promoters and recruit transcriptional initiation components in a stress-specific manner. (opioid-receptors.com)
  • Cdc42 effector proteins were also co-immunoprecipitated with alpha-synuclein from brainstem lysates and were colocalized with alpha-synuclein aggregates in brain sections by double immunostaining. (proteasomesignaling.com)
  • By two-dimensional gel electrophoretic analysis of synaptosomal fractions from transgenic mouse brains we detected additional isoforms of septin 6, a downstream target of Cdc42 effector proteins. (proteasomesignaling.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)
  • The p53 protein is a transcription factor that normally inhibits cell growth and stimulates cell death in response to myriad stressors, including DNA damage (induced by either UV or chemical agents such as hydrogen peroxide), oxidative stress, and deregulated oncogene expression [6-10]. (bioinf.org)
  • According to the International NB Staging Series (INSS), which relies on surgical observations, NB is classified by risk level, tumor location and dissemination, and MYCN (proto-oncogene protein) amplification [ 5 ] . (encyclopedia.pub)
  • The INRG classification takes into account several factors, such as tumor stage and differentiation, patient age, histology, MYCN oncogene status, DNA ploidy, and segmental chromosomal anomalies, in particular chromosome 11q aberration [ 6 ] . (encyclopedia.pub)
  • The p63 protein, a homologue of p53, may be associated with tumor formation in the epithelial tissue, acting as an oncogene 11,12 . (bvsalud.org)
  • Our data suggest that genetic alterations of p53 in tumors are sufficient to promote motility and invasion, thereby contributing to metastasis. (rupress.org)
  • Further accumulation of genetic changes confers invasiveness or metastatic potential on the tumor ( 6 , 7 ), and to date, several indicators have been identified to predict outcomes ( 7 , 8 ). (iiarjournals.org)
  • An important development in cancer research over the past 2 decades has been the recognition that genetic changes drive the pathogenesis of tumors of both adulthood and childhood. (medscape.com)
  • However, these modifications alone may not account in full for p53 stabilization, p53's stability and activity are negatively regulated by the oncoprotein MDM2, whose gene is activated by p53. (tau.ac.il)
  • Phosphorylation at serine 15 of the human p53 tumor suppressor protein is induced by DNA damage and correlates with accumulation of p53 and its activation as a transcription factor. (uthscsa.edu)
  • The DNA-dependent protein kinase (DNA- PK) can phosphorylate serine 15 of human p53 and the homologous serine 18 of murine p53 in vitro. (uthscsa.edu)
  • The activation function-2 (AF-2) domain of ERalpha and the C-terminal regulatory domain of p53 are necessary for the interaction. (nih.gov)
  • ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. (kegg.jp)
  • This activation results in either arrest of the cell cycle in phase G1 or apoptotic cell death, both of which are dependent on the kinase activity of c-Abl. (shengsci.com)
  • Contradictory reports exist about the requirement for DNA-PK in vivo for p53 activation and cell cycle arrest in response to ionizing radiation. (uthscsa.edu)
  • Our results demonstrate that DNA-PKcs, unlike the related ATM protein, is not essential for the activation of p53 and G 1 cell cycle arrest in response to ionizing radiation. (uthscsa.edu)
  • However, the anti-cancer activities and potential anti-cancer mechanisms of the nutraceutical in solid tumors have not yet been elucidated. (bioinf.org)
  • A rise in the levels of the p53 protein induces the expression of p21 cyclin-dependent kinase inhibitor. (reactome.org)
  • We show that loss of the DNA repair protein XPA markedly augments the synthetic lethality between MK2 and p53, enhancing anti-tumor responses alone and in combination with cisplatin chemotherapy. (nature.com)
  • A critical event during tumorigenesis is the conversion from a static primary tumor to an invasive, disseminating metastasis. (rupress.org)
  • Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance. (lookformedical.com)
  • As most human cancers are of epithelial origin (carcinoma), the transcriptional downregulation of adherent/tight junction proteins (e.g. (bvsalud.org)
  • They detected and validated 507 somatic single-nucleotide variants in the tumor, nearly all of which (505) were detected in the MDS sample . (massgenomics.org)
  • Recent studies have found that overexpression of the High-mobility group box-1 (HMGB1) protein, in conjunction with its receptors for advanced glycation end products (RAGEs) and toll-like receptors (TLRs), is associated with proliferation of various cancer types, including that of the breast and pancreatic. (biomedcentral.com)
  • HMGB1 can activate a series of signaling components, including mitogen-activated protein kinases (MAPKs) and AKT, which play an important role in tumor growth and inflammation, through binding to different surface receptors, such as RAGE and TLR2/4. (biomedcentral.com)
  • In this study, we investigated the effect of AKI603, a novel small molecule inhibitor of Aurora kinase A (AurA) to overcome resistance mediated by BCR-ABL-T315I mutation. (scite.ai)
  • The activity of the tumor suppressor protein p53 is controlled by a balance between E3-ligase mediated p53 protein degradation and protein kinase-mediated assembly of p53:p300 transcription machinery. (dundee.ac.uk)
  • MCT-1 oncoprotein accelerates p53 degradation by means of the ubiquitin-dependent proteolysis. (tmu.edu.tw)
  • Since Myc is the common downstream protein of both BCR-ABL and AurA, we proposed the combinational effect of AKI603 and imatinib could be caused by inhibition of Myc. (scite.ai)
  • Inhibition of RNA polymerase II being a cause for the p53 response. (opioid-receptors.com)
  • Combined Aurora kinase and EGFR targeting using a monoclonal anti-EGFR antibody was more effective compared to single EGFR and Aurora kinase inhibition. (oncotarget.com)
  • We found a similar pattern of serine 18 phosphorylation and accumulation of p53 in response to irradiation in both control and DNA-PKcs- null MEFs. (uthscsa.edu)
  • Nuclear p53 protein accumulation was never observed. (ox.ac.uk)
  • Phosphorylations are of vital importance during glycolysis, therefore, making kinases an essential part of the cell due to their role in the metabolism, cell signaling, and many other processes. (wikipedia.org)
  • Ovarian cancer is one of the most aggressive female reproductive tract tumors. (nature.com)
  • Among these miRNAs, we focused on miRNA-31 (miR-31) because miR-31 was the only miR that has been reported to regulate tumor phenotype, an anti-metastatic effect in breast cancer. (nature.com)
  • page 42) paves the way for structure- based drug discovery to target the tumour suppressor p53 protein for potential cancer therapy. (esrf.fr)
  • If some important proteins are mutated or there are defects in the signaling mechanisms, normal cell growth regulation will break down, possibly leading to the occurrence of cancer in the future. (biomedcentral.com)
  • Tumors or cancer of the human BREAST. (lookformedical.com)
  • Tumors or cancer of the OVARY. (lookformedical.com)
  • E6 human papillomavirus lymphadenopathy E7 cu grad ridicat de cervical cancer without high risk hpv se leagă la p53 și PRB și inactivează funcțiile lor cu dereglarea ciclului celular. (asspub.ro)
  • 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)
  • Simple Summary: This study identified a set of 73 microRNAs (miRNAs) that can accurately detect lung cancer tumors from normal lung tissues. (cdc.gov)
  • Based on the consistent expression patterns associated with patient survival outcomes and in tumors vs. normal lung tissues, 10 miRNAs were considered to be putatively tumor suppressive and 4 miRNAs were deemed as oncogenic in lung cancer. (cdc.gov)
  • This study identified a set of 73 microRNAs (miRNAs) that classified lung cancer tumors from normal lung tissues with an overall accuracy of 96.3% in the training patient cohort (n = 109) and 91.7% in unsupervised classification and 92.3% in supervised classification in the validation set (n = 375). (cdc.gov)
  • Based on our identified miRNA-regulated molecular machinery, an inhibitor of PDK1/Akt BX-912, an anthracycline antibiotic daunorubicin, and a multi-targeted protein kinase inhibitor midostaurin were discovered as potential repositioning drugs for treating lung cancer. (cdc.gov)
  • p53 and its transcriptional targets play an important role in both G1 and G2 checkpoints. (kegg.jp)
  • Transactivation of the cyclin-dependent-kinase inhibitor p21, a downstream target of p53, and the G 1 cell cycle checkpoint were also found to be normal in the DNA-PKcs -/- MEFs. (uthscsa.edu)
  • MIF is upregulated in NB tumor tissues and cell lines and it contributes to NB aggressiveness and immune-escape. (encyclopedia.pub)
  • Two proteins involved intimately in regulating cell proliferation are Akt and the tumor suppressor p53 (p53). (bioinf.org)
  • The protein serine/threonine kinase Akt (also known as protein kinase B or PKB) plays an important role in averting cell death. (bioinf.org)
  • p53 has an important protective role against undesired cell proliferation. (bioinf.org)
  • CyclinE is a cell cycle regulatory protein which regulates the G1-S phase transition during cell proliferation. (biomedcentral.com)
  • does retrovirus need to manipulate cell cycle by neutralizing Rb and/or p53? (stackexchange.com)
  • An exception is Ser315 in human p53 (Ser312 in mouse), which is predominantly phosphorylated by cell cycle-related kinases. (ox.ac.uk)
  • According to the risk classification, there are different therapeutic approaches for NB patients, such as observation, surgical tumor removal, chemo- and radiotherapy, autologous hematopoietic stem cell transplantation (AHSCT), differentiation therapy, and immunotherapy [ 7 ] . (encyclopedia.pub)
  • Discordance between the transcriptional activity of p53 and its protein level was further studied using a cell line expressing the p53 reporter plasmid RGC delta fosLacZ. (ox.ac.uk)
  • High-risk E6 and E7 bind to p53 and pRb and inactivate their functions with dysregulation of the cell cycle. (asspub.ro)
  • As a transcription factor whose expression is increased by DNA damage, p53 blocks cell division at the G1 phase of the cell cycle to allow DNA repair. (medscape.com)
  • The p16INK4A protein is a cell-cycle inhibitor that acts by inhibiting activated cyclin D:CDK4/6 complexes, which play a crucial role in the control of the cell cycle by phosphorylating Rb protein. (medscape.com)
  • These proteins help regulate the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion. (medlineplus.gov)
  • In the multicellular theory, each tumor type is associated with a specific differentiated cell of origin within the salivary gland unit. (medscape.com)
  • However, most GEP studies have typically been performed on whole tissue samples, containing varying degrees of tumor cell content, which results in uncertainties in data analysis. (lu.se)
  • B-cell lymphomas (BCLs) constitute a diverse set of tially identify new functional, diagnostic, and therapeutic tumors, both morphologically and clinically, that are mainly targets. (lu.se)
  • Another protein, calgranulin A (Cal A), is involved in the regulation of several cell processes, including the cell cycle and cell differentiation. (bvsalud.org)
  • Other markers, such as retinoblastoma and p53, may be related with early steps of carcinogenesis in oral cavity squamous cell carcinoma. (bvsalud.org)
  • Thus, we demonstrate that phosphorylation of Ser312 is required for p53 to function fully as a tumor suppressor in vivo. (ox.ac.uk)
  • However, this limited expression of ATM protein provides no benefit regarding the ATM-dependent responses related to G1 arrest and p53-ser15 phosphorylation. (nih.gov)
  • This process is associated with posttranslational modifications of p53, some of which are mediated by the ATM protein kinase. (tau.ac.il)
  • The tumor suppressor p53 is a master sensor of stress, and posttranslational modifications are key in controlling its stability and transcriptional activities. (ox.ac.uk)
  • The results indicate that the transcriptional activity of p53 may be negatively regulated. (ox.ac.uk)
  • Our study additionally shows that the majority of AT heterozygotes express almost halved levels of ATM protein, sufficient in most cases to normally regulate the ATM-dependent DNA damage-response pathway. (nih.gov)
  • Furthermore, this is the first report of contraction-induced p53 phosphorylation in human skeletal muscle, thus highlighting an additional pathway by which exercise may initiate mitochondrial biogenesis. (mcmaster.ca)
  • The morphological transition requires the RhoA-ROCK (Rho-associated coil-containing protein kinase) pathway and is prevented by RhoE. (rupress.org)