IndraLab
Statements
sparser
"In that category, the most sensitive and specific biomarker (more properly, “biosignature”) for detecting ovarian cancer currently appears to be a panel of six serum proteins (leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor and CA125), which has been reported to identify ovarian cancer as early as stage I with a striking 99.3% positive predictive value and 99.2% negative predictive value. xref The second biomarker category aims to predict outcome; examples include p53, p21, Ki-67, and HOXA11 DNA methylation. xref – xref The third category is similar to the second but specifically aims to predict which patients will respond to a particular treatment, as is the case for the biomarker upon which this review is focused."
sparser
"It would also be of interest to examine how cytosine methylation at the 5′-C of the CpG sites at Fapy•dG 248 and 273 may influence replicative bypass of Fapy•dG, as we have shown previously that in p53 codon 273 cytosine methylation increases MF of a bulky dG adduct significantly [ xref ]."
sparser
"PCMT1 can interact and negatively regulate the tumor suppressor protein p53 (reduced protein level and activity) by carboxyl methylation of p53 at isoaspartate residues 29 and 30, which in turn represses apoptosis and growth arrest and contributes to cancer progression [ xref ]."
sparser
"Acetylated p53 may have an increased ability to transcribe BAX, but not CDKN1A, resulting in a preferential activation of the apoptotic pathway over cell cycle arrest, while methylated p53 may have an increased ability to transcribe CDKN1A, resulting in a preferential induction of cell cycle arrest [ xref , xref ]."
sparser
"Taken together, long-term Se consumption not only affects selenoprotein enzyme activities, homocysteine, tissue Se concentrations, and global genomic DNA methylation but also increases exon-specific DNA methylation of the p53 gene in a Se-dose-dependent manner in rat liver and colon mucosa."
sparser
"The p53K372me1 modification leads to p53-dependent transcriptional activation. xref Interestingly, the SET7-mediated p53K372me1 modification prevents methylation by SMYD2 on K370 and repression of p53 activities. xref However, the SMYD2-mediated methylation of p53, p53K370me1, does not affect SET7 activity on p53. xref The p53-bound SMYD2 structure was resolved and highlights several interactions between p53K372 and SMYD2 SET domain, including an hydrogen bond between p53K372 ε-amine group and the carbonyl of SMYD2 valine 215. xref Therefore suggesting that p53K372me1 could sterically hinder the interaction of p53K372 with SMYD2 valine 215 and impair the methylation of K370 by SMYD2. xref "
sparser
"Another recent study of newborns in Thailand showed that arsenic-exposed newborns had significantly higher levels of arsenic in cord blood, fingernails, toenails, and hair and a slight increase in promoter methylation of p53 in cord blood lymphocytes compared to the newborns of arsenic-unexposed mothers ( xref )."
sparser
"Response: As instructed the sentence has been reframed and corrected as “When we considered the cases where changes in p53 promoter methylation was observed, the differences in methylation profile indicated that p53 promoter hyper-methylation was significantly associated lower severity grade (stage IIA and IIB)” and has been incorporated in the text and same has been highlighted in blue oion the text"
sparser
"While p53 methylation was not found in any of the samples tested, differences in DNA concentration between the two groups may shed light on the timing of epigenetic alterations, as well as better explain why the negative impact of smoking is not often found in young, healthy adults."
sparser
"The primary substrate of PRMT3 is 40S ribosomal
protein S2 (rpS2). xref , xref Asymmetric dimethylation of
rpS2 by PRMT3 results in stabilization of rpS2 and influences ribosomal
biosynthesis. xref − xref PRMT3 has also been reported to methylate the recombinant mammalian
nuclear poly(A)-binding protein (PABPN1) xref − xref and a histone peptide (H4 1–24) in vitro. xref The protein complex consisting of PRMT3, the von Hippel-Lindau
(VHL) tumor suppressor, and ARF (alternative reading frame) has been
shown to methylate the tumor suppressor p53. xref In addition, the tumor suppressor DAL-1 (differentially expressed
in adenocarcinoma of the lung-1) inhibits the methyltransferase activity
of PRMT3 by interacting with it, suggesting that DAL-1 may affect
tumor growth by regulating PRMT3 function. xref Epigenetic downregulation of DAL-1 has been associated with a number
of cancers. xref − xref Furthermore, PRMT3 expression levels are
elevated in myocardial tissues from patients with atherosclerosis, xref potentially implicating the involvement of
PRMT3."
sparser
"Interestingly, while the KIE-constrained TS of the SET7/9-catalyzed H3K4 methylation is in modest agreement with the symmetrical TS via quantum mechanics/molecular mechanics (QM/MM) simulation (2.2~2.3 Å C–S and C–N distances), xref the KIE-constrained TS of the SET7/9-catalyzed p53 methylation is significantly different from the late S N 2 TS solely determined by QM/MM (C–S distance: 2.6 Å; C–N distance: 2.0 Å). xref In addition, the KIE-constrained S–N distances of 4.2~4.3 Å are 0.3 Å shorter that those solely simulated with QM/MM."
sparser
"PFI-5 inhibits methylation of p53 in MCF7 cells with an IC 50 of 1.3 μM. Additionally, PFI-5 shows less than 20% inhibition against a panel of 33 protein lysine methyltransferases (PKMTs), PRMTs, DNMTs, and RNMTs when tested at 50 μM. The PKMTs SUV420H1 and SUV420H2 were the only enzymes that showed partial inhibition in the presence of 1 μM of PFI-5."
sparser
"Davis et al. have demonstrated that in the colon and liver, selenium deficiency causes global hypomethylation and in addition, promoter methylation of p53 and p16 genes, suggesting that impacting DNA methylation may be a crucial mechanism of selenium for cancer prevention [ xref ]."
sparser
"Steady-state levels of p53 mRNA correlated directly with plasma and colonic folate concentrations (P = 0.41-0.49, P < 0.002) and inversely with plasma homocysteine and colonic SAH levels (r = -0.37-0.49, P < 0.006), but did not significantly correlates with either genomic or p53 methylation within the promoter region and exons 6-7."
sparser
"Results showed that arsenic-exposed newborns had significantly higher levels of arsenic in cord blood, fingernails, toenails and hair than those of the unexposed subjects and a slight increase in promoter methylation of p53 in cord blood lymphocytes which significantly correlated with arsenic accumulation in nails (p < 0.05) was observed, while LINE-1 methylation was unchanged."
sparser
"Molecular analysis of lymphomas, revealed that arginine methylation of p53 selectively suppresses expression of crucial proapoptotic and anti-proliferative target genes thereby sustaining tumor cell self-renewal and proliferation and bypassing the need for the acquisition of inactivating p53 mutations."
sparser
"We further analyzed the relationship between p53 status and DLEC1 methylation or expression using TCGA database cohorts, and found that wild-type p53 is significantly correlated with DLEC1 high expression/low methylation, supporting our findings of p53 regulation of DLEC1 promoter (Fig. xref D, E)."
sparser
"Proteome-wide
methylation of
lysine residues is an enzymatic posttranslational modification with
multifaceted biological outcomes. xref , xref This process
is catalyzed by protein lysine methyltransferases (PKMTs), which deposit
the sulfonium methyl group of the cofactor S -adenosyl- l -methionine (SAM) on diverse histone and nonhistone targets. xref , xref Among more than 50 PKMTs encoded by the human genome, SETD8/SET8/Pr-SET7/KMT5A
is the sole PKMT known for the in vivo monomethylation
of histone H4 lysine 20 (H4K20me1). xref , xref The level of
the SETD8 protein is finely tuned by multiple E3 ligases throughout
a cell cycle with the highest level at G2/M phase and the lowest level
at S phase. xref − xref Disruption of endogenous SETD8, accompanied by suppression of H4K20
monomethylation, leads to cell cycle defects, chromatin decondensation,
and enlarged nuclei, indicating the essential role(s) of SETD8 in
DNA replication. xref − xref SETD8 also methylates nonhistone targets such as proliferating cell
nuclear antigen (PCNA), the tumor suppressor p53, and the p53-stabilizing
factor Numb. xref − xref Methylation of p53 or Numb results in the downregulation
of apoptosis either by antagonizing p53 acetylation, which is required
for p53-mediated transcriptional activation, or promoting p53 ubiquitination
for degradation. xref , xref These findings associate the
functions of SETD8 with transcriptional regulation and DNA damage
response."
sparser
"Results showed TP53 gene promoter was partially methylated (63%) in D0 group and then anchorage blockade promoted significant hypermethylation in groups D1 and D3 (92% and 95%, respectively) and hypomethylation in D5 and D24 if compared to TP53 methylation pattern of HaCaT anoikis-resistance cell to control group (D0) ( xref B)."
sparser
"Genetic variation in TERT , TRF1, TRF2, POT1, TEP, TNKS1, TNKS2, TP53, ATRX and DAXX [ xref – xref ] and aberrant promoter methylation of TERT , WRN , POT1, RAD50 and TP53 [ xref – xref ] have been reported to contribute to the dysregulation of telomere length and telomerase activity in breast cancer."
sparser
"AuNP exposure had dose-specific changes in promoter methylation of Gsr (CpG#4 and CpG#6, p = 0.018 and p = 0.012, respectively), Pparg (CpG#3, p = 0.031) and tumor protein P53 ( trp53 ) (CpG#1, p = 0.028) with low and high dose, 60 and 250 nm, respectively (i.e., dose effect) ( xref , xref )."
sparser
"To probe the importance of p53 methylation for the PHF20–p53 interaction in vivo , we checked whether mutations that affect the interaction of PHF20 Tudor2 with p53K370me2 or p53K382me2 peptides but preserve the Tudor domain fold would alter the affinity of PHF20 for p53 in the context of full-length proteins."
sparser
"The meta-analysis of WIF1 gene methylation was performed between HCC tumor tissues vs adjacent tissues and HCC serums vs normal serums, and the meta-analysis of DLC1 , p53 , SPINT2 , RB1 , OPCML and WT1 genes methylation was performed between HCC tumor tissues vs adjacent tissues."
sparser
"The correlation between aberrant oncogene-induced arginine methylation of p53 accompanied by a progressive decline in PRMT5 and the short-lived oncogenic stress response in FA HSPCs prompted us to determine whether restoring the level of PRMT5 could lengthen the oncogenic response in FA HSPCs."
sparser
"Several pathways known to be involved in colonic cell differentiation were differentially expressed between surface epithelium and the crypt compartments, including the WNT/β-catenin, TGF-β and G1/S cell cycle checkpoint, as well as the mTOR, TP53 and DNA methylation and double-stranded break repair pathways xref , xref , xref , xref , xref , xref , xref , xref , xref , xref ( xref and xref )."
sparser
"Selenium is an essential trace element with both anti-oxidant and pro-apoptotic properties. xref , xref Davis et al. xref have demonstrated that in the colon and liver, selenium deficiency causes global hypomethylation and in addition promotes methylation of p53 and p16 genes, suggesting that impacting DNA methylation may be a crucial mechanism of selenium for cancer prevention."
sparser
"Interestingly, a few tumors that exhibited no activity from any of these three promoters still expressed BORIS transcripts (data not shown), suggesting the possible existence of additional regulatory sequences that act upstream of promoter A. Thus, DNA methylation, and expression of CTCF and p53 represent three mechanisms involved in the negative regulation of BORIS transcription, although it seems likely that additional levels of control also exist."
sparser
"Many genetic alterations are been considered as actionable in breast cancer tumorigenesis and progression, such as mutations of TP53,KRAS, PIK3CA, and promoter methylation of breast cancer-related genes including APC, BRCA1, ER1, GSTP1, HIN1, RARβ, RASSF1 and TWIST [ xref – xref ]."
sparser
"The positive rates of methylation of p53 gene (exon 5) were 55.26% (21/38), 51.16% (22/43) and 48.39% (15/31) respectively among mild, moderate and severe arsenism group, which were obviously lower than the rates in the control group (88.88% (80/90), χ² values were 18.151, 23.168, 22.420, respectively, both P values < 0.017)."
sparser
"To address to the question whether promoter methylation of novel p53 effector genes is a common event in transitional cell carcinoma of the bladder, we selected the p53 target genes apoptotic protein-activating factor (APAF-1), Caspase 8 (CASP-8), death-associated protein kinase, (DAPK-1) and insulin-like growth-factor-binding protein-3 (IGFBP-3), performing quantitative methylation-specific real-time PCR."
sparser
"Significant correlation between G:C --> A:T transitions in the TP53 gene and promoter methylation of the O6 -methylguanine-DNA methyltransferase (MGMT) gene in glio-mas have been reported in several studies, suggesting the possible involvement of O6-methylguanine DNA adducts, which may be produced by exogenous or endogenous alkylating agents in the development of gliomas."
sparser
"Functional ingredients of blueberry restrain the growth and metastasis of breast cancer cells by modulating the PI3K/AKT/NF-κB pathway [ xref ]; the expression of caspase-9 and cytochrome c as well as the downregulation of the methylation of p53 of blueberry anthocyanins suppressed the proliferation and induced G2/M cell arrest and oral cancer cells apoptosis [ xref ]."
sparser
"The positive rates of methylation of p53 gene in promoter region were 13.16% (5/38), 27.91% (12/43) and 45.16% (14/31) respectively among mild, moderate and severe arsenism group, which were obviously higher than the rates in the control group (1.11% (1/90), χ² values were 8.679, 23.690, 41.199, respectively, both P values < 0.017)."
sparser
"The short recognition sequences enable these two enzymes to methylate many nonhistone substrates, including Set7/9-mediated methylation of p53 [ xref ], components of the TBP complex, TAF10 [ xref ] and TAF7 [ xref ], estrogen receptor α [ xref ], DNA methyltransferase 1 [ xref ], and G9a-mediated methylation of chromodomain Y-like protein (CDYL1) and widely interspaced zinc finger motifs protein (WIZ) [ xref ], CCAAT/enhancer-binding protein-β(C/EBPβ) [ xref ], as well as G9a auto-methylation [ xref ]."
sparser
"In conclusion, the present study, using an innovative in vivo model integrating the stress-responsive Gadd45β -luciferase transgene and inducible oncogenes (LSL-K-ras G12D and Myc ER ), uncovers two novel and significant findings: (i) normal HSPCs utilize arginine methylation of p53 by PRMT5 to orchestrate long-lasting oncogenic response. (ii) FA deficiency leads to a complete reversal of the response pattern characterized by short-lived oncogenic stress response accompanied with aberrant oncogene-induced arginine methylation of p53 resulted from a progressive decline in PRMT5 in FA HSPCs."
sparser
"The clinical relevance of this model is emphasized by the demonstration that concurrent elevation of PRMT5 and p53 arginine methylation occurs in primary human cancers such as mantle cell lymphoma and esophageal squamous cell carcinoma, two cancers where cyclin D1 is considered a driver oncogene."
sparser
"In the present study, we have examined the serum level of folate, promoter methylation status of frequently methylated tumor suppressor genes p16 and p53 using blood samples, and investigated the intake of foods rich in folate via a validated qualitative FFQ among healthy controls, EPL cases, and ESCC cases."
sparser
"Using a homologous integration method, the present study asks whether changes in intragenic TP53 methylation are dynamically inducible, whether such changes correlate with altered TP53 isoform expression, and whether patterns of TP53 intragenic methylation and/or isoform expression differ between normal and cancer cell systems."
sparser
"Indeed, p53 modification events can be observed on the promoter of the p21 gene, a known transcriptional target of p53, resulting in its transcriptional activation via acetylation leading to subsequent cell cycle arrest. xref Further investigation has identified Tip60 as the p53 specific acetyltransferase and demonstrated mechanistic link between methylation and acetylation of p53. xref Similarly, methylation TAF10 at K189 potentiates transcription of a set of RNA Pol II dependent genes."
sparser
"The accessibility of Lys370, the natural target site for Smyd2‐mediated p53 methylation, to the cofactor was assessed by calculating the distance between the amino group of Lys370 and the sulfur atom of AdoMet/AdoHcy that acts as the methyl donor (boxplot representation in Fig. xref D)."
sparser
"The positive rates of methylation of p53 gene (exon 5) were 54.17% (13/24) and 42.11% (8/19) in non-cancerous and cancerous group respectively, which were obviously lower than those in the control group (88.88% (80/90), χ² values were 15.201, 22.075, respectively, both P values < 0.025)."
sparser
"The majority of TP53 -related drug development efforts have been directed towards designing therapies to exploit cancer-specific vulnerabilities associated with dysregulation of TP53 , such as del17p, TP53 mutations, TP53 promoter methylation, and MDM2 overexpression [ xref , xref ]."
sparser
"Unfortunately, most current circulating breast cancer markers, including serum tumour markers (CA15-3, CA27.29, CEA), circulating cancer DNA or cell-free DNA (mutation of TP53, KRAS, PIK3CA and promoter methylation of APC, BRCA1, TWIST) and circulating tumour cells (CTCs), exhibit low sensitivity xref – xref ."
| PMC
sparser
"Two weeks of treatment with arsenite showed no effect on p53 promoter methylation in the lymphoblast cell line, but a dramatic increase (approximately 300 % of the control level) was observed at four weeks (p < 0.05 and p < 0.01 at arsenite concentrations of 0.5 and 1.0 μM, respectively), with a subsequent decrease to control levels by six weeks."
sparser
"Our previous and present data show alterations of at least one of TP53 promoter methylation, p14ARF promoter methylation, and TP53 mutations in 43/49 (88%) of low-grade astrocytomas, 15/18 (83%) of oligoastrocytomas, and 35/42 (83%) oligodendrogliomas, suggesting that disruption of the TP53/p14ARF pathway is frequent in all histological types of low-grade glioma."
sparser
"In repeated measures linear regression of 9 CpG sites of Tp53 , taking into account their covariance and adjusting for sex and CpG site, Tp53 methylation was statistically significantly lower in both exposure groups compared to unexposed (estimate of −1.09 ± 0.34%, p = 0.002 for low and −0.91 ± 0.34%, p = 0.01 for high)."
sparser
"However, some mechanisms have been recently identified, including arginine methylation of the tumor suppressor p53, that inhibits p53-mediated apoptosis.[ xref ] Furthermore, PRMT5 supports constitutive CYCLIN D1/CDK4/6 activity leading to inactivation of the RBL2/E2F tumor suppressor pathway ( 8 )."
sparser
"Our results suggest that cell death induced by PRMT5 silencing occurs independent of P53 mutational status indicating that the relevance of arginine methylation of P53 may differ between tumor types and, perhaps, PRMT5 might serve as an equally attractive target in GBM tumors where P53 is often mutated or deleted and associated with a poor prognosis."
sparser
"Because the PIMT-mediated methylation of p53 could directly regulate the interaction between HDM2 and p53, PIMT might act as a regulator for the maintenance of p53 steady-state levels, and the interaction of p53 and HDM2 could be regulated through the PIMT-mediated methylation of isoaspartyl residues."
sparser
"Besides MDM2, other ubiquitin ligases such as RIPH2, COP1, and CHIP have also been identified as negative regulators of p53. xref Apart from ubiquitination, phosphorylation, acetylation, sumoylation, or methylation of p53 has been demonstrated to promote p53 stabilization and activation. xref Once p53 is activated, expressions of genes involved in cell cycle mediation, cell apoptosis or senescence induction, or tumor angiogenesis are induced by p53. xref "
sparser
"That p53 can be methylated and demethylated by HMTs and HDMs, respectively, not only reveals new roles of HMTs and HDMs other than histone methylation but also demonstrates the molecular similarity between histone modification and their non-histone substrate methylation xref xref ."
sparser
"In this study, we attempted to investigate the gene-nutrition interaction with folate and aberrant DNA methylation in the different stages of carcinogenesis of ESCC by detecting serum folate level, promoter methylation status of frequently methylated tumor suppressor genes p16 and p53, and evaluating the intake frequency of foods rich in folate among healthy controls, EPL cases, and ESCC cases."
sparser
"SMYD2 is mostly cytoplasmic where it catalyzes mono-methylation of p53, xref retinoblastoma protein (Rb), xref estrogen receptor α (ERα), xref and heat shock protein 90 (Hsp90). xref Recent proteomic analysis found numerous substrate proteins of SMYD2, suggesting its roles in diverse cellular processes. xref Importantly, both SMYD1 and SMYD2 are abundant in cardiac and skeletal muscle, playing an important role in myofibril assembly. xref At a molecular level, SMYD2 forms a complex with Hsp90. xref This complex binds to the N2A domain of titin at the I-band of sarcomere. xref Recently, it was found that zebrafish with knockdown of SMYD2 (a or a/b isoforms) forms disorganized I-bands and Z-disks in the sarcomere of muscle, xref suggesting its role in sarcomere stabilization."
sparser
"In addition to p53 methylation, a new study showed that the retinoblastoma tumor suppressor (RB), a central cell cycle regulator and tumor suppressor, can also be methylated by SmyD2 at lysine 860, which regulates the RB activity during cell cycle progression, cellular differentiation, and in response to DNA damage xref ."
sparser
"To determine if Smad7 contributes to healing in human oral keratinocytes, we knocked down Smad7 in spontaneously immortalized human oral keratinocytes (NOK-SI) xref , which harbor a p53 (R283Q) mutation andp16 INKa promoter methylation but no mutations in any of the TGF-β signaling components (unpublished data from Gutkind laboratory)."
sparser
"When we considered the cases where changes in p53 promoter methylation was observed, the differences in methylation profile indicated that p53 promoter hyper-methylation was significantly associated lower severity grade (stage IIA and IIB) compared to higher severity grade (≥stage III) of CaCx cases (p = 0.036); which correlates with the expression pattern of P53 at mRNA and protein level, and underlines the significance of methylation in p53 biology in CaCx."
sparser
"For example, profiling of LLY-507 in multiple panels of cancer cell lines in both standard and longer duration proliferation studies revealed that 1) the catalytic function of SMYD2 plays a role not only in ESCC but in HCC and breast cancer cell proliferation and that 2) the sensitivity of tumor cell proliferation to inhibition of SMYD2 catalytic function does not depend on levels of SMYD2 expression or the methylation of either p53 or Rb."
sparser
"We noticed that the effect of p53 methylation on its transcriptional activities was mainly examined in cells with wild type p53. xref Since both MDA-MB-231 and Hs587T cells solely express mutant p53, KDM3A knockdown unexpectedly revealed that increasing p53-K372me1 could reactivate mutant p53 to induce the expression of pro-apoptotic genes."
sparser
"Since then, DNA methylation of TP53 gene or its regulatory sequences have been reported in many cancers including Ewing’s sarcoma [ xref ], glioblastoma [ xref ], acute lymphoblastic leukemia (ALL) [ xref , xref ], human hepatocellular carcinoma [ xref ], ovarian cancer [ xref ], breast cancer [ xref ] and also in MM [ xref , xref ]."
sparser
"Recent studies suggested that several molecular factors, such as genetic instability, epigenetic alteration, immune response, oxidative stress and microbiota, contribute to the pathogenesis of CRC in patients with UC. xref Considering the mechanism of developing CRC in UC, molecular alterations in particular, such as genetic alteration including genetic mutations, microsatellite instability, DNA methylation and loss of heterozygosity of p53, would play an important role in the pathogenesis of CRC in patients with UC. xref xref To detect CRC at an early stage certainly, therefore, those molecular alterations in biopsy specimens taken from colonic mucosa with a targeted biopsy method should be evaluated."
sparser
"A variety of in vitro studies and animal studies have been performed to identify the chemopreventive mechanisms of blueberries. xref Beyond the antioxidant properties, blueberry anthocyanins induced G2/M cell cycle arrest and apoptosis of oral cancer cells by downregulating methylation of p53. xref Moreover, anthocyanin-rich food including blueberry showed a significant role on vessel endothelium and had an enhanced effect in decreasing the risk of myocardial infarction. xref However, chemopreventive mechanisms of blueberry in human are not clarified yet."
sparser
"Me C is an important endogenous DNA modification that plays an major role in many cellular processes. xref All CG dinucleotides within the coding sequence of the p53 tumor suppressor gene are methylated, and the same sites are frequently mutated in smoking-induced lung cancer. xref , xref Methylation of the C-5 position of cytosine can influence the local DNA structure and the electronic environment within Me CG dinucleotides. xref "
sparser
"Phospholipase C epsilon 1 (PLCE1) is the most essential member of the phospholipase family. xref PLCE1 catalyses the hydrolysis of phosphatidylinositol 4,5‐bisphosphate to generate two secondary messengers inositol 1,4,5‐triphosphate and diacylglycerol. xref These products subsequently initiate a cascade of intracellular responses that result in cellular proliferation, differentiation and apoptosis. xref In addition, PLCE1 is a suppressor of P53 by promoting p53 promoter methylation. xref To date, many studies have reported that PLCE1 may play an essential role in carcinogenesis and progression of various human cancers, including oesophageal cancer, xref lung cancer, xref colorectal cancer (CRC) xref and hepatocellular carcinoma. xref However, little information has been reported regarding the regulation of PLCE1 protein in tumours."
sparser
"Similarly, increased TP53 methylation in the IDH-mutant group did not seem to affect the gene expression, and, furthermore, genes that negatively regulate TP53 (i.e., MDM1, MDM2, and MDM4 ) were all expressed at significantly lower levels in IDH-mutant glioma than in IDH-wildtype glioma."
sparser
"Further to the aforementioned studies on gene expression, the present study was conducted in the cord blood samples from the same studied groups to examine the effects of arsenic exposure in utero on DNA methylation, focusing on global DNA methylation and p53 promoter methylation in cord blood lymphocytes of newborn babies."
sparser
"However, a variety of post‐transcription modifications of p53 have been found to be associated with its stability. xref Thus, cytoplasmic irradiation might result in acetylation, methylation, or phosphorylation of p53 and its destabilization, which should be further investigated."
sparser
"In this regard, it has been reported that SMYD2 can methylate p53 on Lys 370 and that this methylation leads to repression of its activity. xref As p21 is also a key mediator of p53-dependent cell cycle arrest, SMYD2-mediated p53 methylation and inactivation may decrease expression of p21 expression, thereby increasing activation of CDK4 and CDK6 and expression of cyclinD1, promoting cell cycle progression."
sparser
"By adding the striking TP53 methylation marker to a prognostic MDS patient transplantation outcome panel test composed of even a dozen of the top prognostic markers from previous studies, the potential algorithm could be improved over assays and technologies that seek to measure hundreds to thousands of markers."
sparser
"In this study, we aimed to further clarify the mechanism of inactivation of TP53 in GAED in the light of promoter methylation of TP53, and expression of methylation-associated proteins such as Ten-eleven translocation (TET) 1 and 5-hydroxymethylcytosine (5-hmc) in addition to ATM mutations."
sparser
"Knockdown of the Caenorhabditis elegans p53 gene (Cep-1) can increase lifespan. xref Furthermore, an epidemiological study showed that a mutation in the p53 protein (R72P) increases survival and contributes to aging. xref Recent data have suggested that p53 is an important inducer of organismal aging; for example, p53-mediated skin aging involves the loss of subdermal fat and declining sebaceous gland activity. xref In our study, we found that methylation of the p53 promoter was significantly altered after alterations in miR-377 expression in HSFs."
sparser
"The p53 protein is also monomethylated at K382 (p53K382me1) by SET8. xref In the context of DNA damage signaling induced by neocarzinostatin, the levels of p53K382me1 are reduced. xref The methylation of p53 by SET8 leads to reduced p53-dependent expression of p21 . xref Interestingly, L3MBTL1 binds to p53K382me1 to silence the expression of p21 under normal conditions, but upon induction of DNA damage, p53 is relieved from L3MBTL1. xref Summarily, the p53K382me1 mark provides a docking site for the transcriptional silencer L3MBTL1 and upon genotoxic stress, reduced p53K382me1 level are relieving L3MBTL1 from p53, thereby allowing p53-dependent transcriptional activation."
sparser
"The analysis performed using structural equation modelling (SEM) further throws light on the causal relationship between sustenance of pregnancy or URSA during the first trimester of a human pregnancy and degree of methylation of p53 which is closely correlated with the interaction between G9aMT, DNMT1, BCL-2, BAX, P53, CASPASE-6, and apoptosis."
sparser
"Given that previous mass spectrometry revealed that Fbox22 formed a stable complex with KDM4A xref and that SCF Fbxo22 preferentially targeted methylated p53, we speculated that SCF Fbxo22 might form a ternary complex with p53 and KDM4A. Wild-type Fbxo22 and its mutant lacking FIST-N bound to KDM4A, whereas the mutant lacking FIST-C failed to do so ( xref ), indicating that the FIST-C domain of Fbxo22 is a KDM4A-binding site."
reach
"By using epigenetic chromatin modification enzymes PCR Array, gene expression microarray, RT-PCR and Bisulphite sequencing, the results show that berberine can repress the expression of DNMT1 and DNMT3B, which triggers hypomethylation of TP53 by changing the DNA methylation level and the alteration of p53 dependent signal pathway in human multiple melanoma cell U266."
sparser
"Lysine methylation has been associated with the regulation of protein-DNA interactions since early studies characterizing non-histone lysine methylation on the tumor suppressor protein p53 ( xref ), and this has been confirmed to be a major mechanism by which lysine methylation impacts protein function ( xref )."
sparser
"For instance, over-expression of EZH2, the only known H3K27 methyltransferase, was common in human HCC tissues, and transcriptional silencing of CXCR4 by EZH2-mediated H3K27me3 was correlated with a poor prognosis in HCC patients. xref Copy number gain of SETDB1, a histone H3K9 methyltransferase, was reported to regulate the growth of HCC cells through methylation of a well-known tumor-suppressor p53. xref Nevertheless, the role of distinct histone KMTs and KDMs in the pathogenesis and development of HCC remains unorganized."
sparser
"H4K20 monomethylation (H4K20me) has been shown to regulate the DNA damage response, the cell cycle, and chromatin condensation. xref , xref , xref The role of H4K20me in transcription is unclear; it has been associated with both activation and repression. xref SETD8 also catalyzes methylation of the cancer-related proteins proliferating cell nuclear antigen (PCNA) and p53. xref Methylation of p53 by SETD8 suppresses p53-mediated transcriptional activation. xref SETD8 knockdown enhances the proapoptotic function of p53."
sparser
"The complex is located at the promoters of heat shock genes and is required to prevent apoptosis. xref A physical interaction of TTC5 with Protein Methyltransferase 5 (PRMT5), which arginine methylates TP53, has been reported, xref as has a regulatory role for TTC5 in steroid hormone signaling where it acts as a cofactor for the glucocorticoid and estrogen receptors. xref "
sparser
"Originally defined as a critical layer of p53 regulation in human cell lines, p53 lysine methylation by Set7/9 (also called Setd7) was proposed to fulfill a similar function in vivo in the mouse, promoting p53 acetylation, stabilization, and activation upon DNA damage (Kurash et al., 2008)."
sparser
"Interestingly, the K to A substitution, but not the K to Q substitution, at all five lysines as well as at two lysine sites at which p53 was methylated did not affect their interactions, suggesting that substitution at these lysines did not result in marked conformational changes in the p53 CTD domain."
sparser
"In multiple myeloma (MM) KAS 6/1 cells, IL-6 treatment leads to TP53 promoter methylation, resulting in decreased TP53 expression levels. xref Therefore, increased autocrine IL-6 expression in PAX5 − MCL cells may contribute to the reduction in TP53 gene expression via promoter hypermethylation."
sparser
"This low catalytic activity has been attributed to a splayed
configuration between the Rossmann fold domain and the metal binding
domain. xref Posttranslational modifications such as ubiquitination, methylation and acetylation
of p53 have been suggested to dictate its tumor suppressor function. xref , xref Acetylated lysine 382 has been identified as the endogenous
substrate of HDAC1 xref and
SIRT1. xref , xref Deacetylation at this specific lysine
residue can cause ubiquitin-dependent p53 degradation, xref and ultimately reduces its transcriptional
activity. xref , xref Another speculative function of p53
acetylation is to recruit deacetylases for targeted gene repression. xref The regulation of p53K382
acetylation remains largely elusive."
sparser
"Our results did not show alteration of p53 DNA methylation, although we did identify PM 2.5 associated changes in methylation of of CDK2AP1 (associated with lung and nasopharyngeal carcinomas), ( xref ; xref ) SFRP2 (modulator of lung cancer cell apoptosis) ( xref ), and PLCH1 (associated with non-small cell lung cancer risk) ( xref )."
sparser
"Normally, CTCF, p53, and CpG methylation suppress BORIS transcription in somatic cells, effectively restricting its expression to testicular germ cells xref , xref , where the absence of CTCF xref and several waves of genome-wide demethylation create the conditions for BORIS activation."
sparser
"The interactions of not consuming any Chinese cabbage or livers with p16 or p53 methylation was significantly associated with an increased risk of EPL or ESCC ( p for interaction < 0.05), whereas the association between p16 or p53 methylation and EPL or ESCC risk was not statistically significant for those that consumed Chinese cabbage or livers once per week or more ( p for interaction > 0.05)."
sparser
"Lysine (K) and arginine (R) residues in p53 can be methylated, and a growing number of studies in recent years have shown that p53 methylation takes place during the DNA damage response. xref – xref Methylation of lysine and arginine residues in histones has long been known to impact chromatin structure and gene expression. xref In recent years, the methylation of p53 has emerged as an important modification that affects its function in various processes, such as cell cycle arrest, DNA repair, senescence, apoptosis, and tumourigenesis. xref Whether p53 is activated or depressed depends on the location of the modification and the number of methyl groups attached. xref Protein arginine N -methyl transferase 5 (PRMT5) was first shown to methylate p53 at several arginine residues (R333, R335, and R337) in the tetramerization domain, xref which specifically controls the functions of p53 in cell cycle arrest and is suggested to inactivate p53 during lymphomagenesis. xref , xref There are three different lysine methyl transferases (KMTs) that could mono-methylate p53, and there are at least two KMTs could di-methylate p53. xref "
sparser
"However, repressive K382 methylation prevents acetylation by CBP/p300 at this same site, and the level of methylation at K382 decreased upon DNA damage, counteracting its inhibitory effect and promoting CBP/p300-dependent acetylation of K382. xref Thus, the interplay between p53 methylation, and phosphorylation, as well as acetylation, demonstrates a mechanism for modulating p53 transcriptional activity upon stress."
sparser
"Although mean methylation levels were significantly lower in tumor tissues as compared to normal tissues for all of the markers suggesting higher apoptotic activity, in individual tumors we found that higher levels of methylation of the combined markers Apaf1, Bcl2 and p53 correlated to shorter patient survival and recurrence-free periods as compared to the patients showing low expression of one or two of the markers."
sparser
"Further, in myeloma cells, IL-6-dependent STAT3 signaling has been found to drive methylation and deactivation of the critical tumor suppressor gene p53, allowing cancer cells to bypass crucial checkpoints that regulate cell cycle progression and evade apoptotic signals resulting from DNA damage [ xref ]."
sparser
"Using in silico expression analysis of microarray data from colonic biopsy samples (Affymetrix HGU133Plus2.0 GEO accession numbers: GSE37364 [ xref ], GSE18105 [ xref ], GSE4107 [ xref ], GSE9348 [ xref ], GSE22242 [ xref ], GSE8671 [ xref ]), an inverse relation between promoter DNA methylation alteration and mRNA expression (Table xref ) was shown for a number of differentially methylated TP53 pathway genes including CDKN1A , CDKN2A , GTSE1 , IGFBP3 , SESN2 and SESN3 (Table xref )."
sparser
"Furthermore, the difference in p53 methylation betweenApc +/Min and WT mice was also observed in adults (mean 96 days of age), indicating that these epigenetic changes are sustained during the period of development of macroscopic tumors (see McKay et al., xref for details of tumor size and multiplicity)."
sparser
"Although the mechanism linking these methyltransferases and CK is unknown, it noteworthy that SMYD2 may act as an oncogene by promoting the methylation of p53 and of the retinoblastoma tumor suppressor protein (RB) [ xref – xref ], and that SMYD3 promotes MAP3K2 methylation, inducing genomic instability by activation of Ras/Aurora kinase A-driven mechanisms [ xref , xref – xref ]."
sparser
"In non-cancerous cells the heparanase promoter is constitutively inhibited secondary to promoter methylation and activity of wild type p53, which suppresses transcription of the heparanase gene by directly binding to its promoter. xref Furthermore, additional regulation occurs during post-translational processing."
sparser
"Recent studies suggest that in addition to modulation of histone substrates, KDM1 associates with p53 and regulates its function by demethylation [ xref ] and that the interplay between p53 methylation and acetylation provide mechanisms for triggering a rapid increase in p53 transcriptional activity."
sparser
"Similar to D1T286A, we noted increased p53 methylation on arginines targeted by PRMT5 in NOTCH and MLL-AF9 triggered tumors, but not those generated by c- MYC expression, suggesting that PRMT5 may contribute to p53 inactivation in tumors where NOTCH or MLL-AF9 function as drivers, thereby alleviating selection for p53 mutation."
sparser
"Arsenic pollution caused by coal-burning can cause the hypermethylation of p53 gene in promoter region, hypomethylation and mutation of p53 gene (exon 5), and the changes of methylation of p53 gene are related with its mutation and might be one of the important etiological factors of arsenic pathogenicity or carcinogenesis."
sparser
"Here, we measured relative protein levels of seven histone methyltransferases (SMYD2, SETD7, ASH2L, RBBP5, SUV39H1, EHMT2, and SET8), four methylated histone H3 residues (H3K4me1, H3K9me3, H3K27me1, and H3K36me2), the methyltransferase activity on H3K4, and methylation of p53 (p53K370me2 and p53K372me1) in the skeletal muscle and liver of the freeze-tolerant wood frog (Rana sylvatica) during the freeze-thaw cycle."
sparser
"For instance, the methylation of p53, TAF10, AR, ERα and pRb enhances their corresponding activities by improving protein stability or via other mechanisms ( xref , xref , xref , xref , xref – xref ); by contrast, the methylation of DNMT1, Stat3, Yap, Foxo3a and Suv39h1 impairs their corresponding activities ( xref , xref – xref )."
sparser
"To elucidate that DNA methylation of FOXO3 and TP53 is associated with the severity or exacerbation of LOA, we further analyzed the correlation between the 8 DMSs and lung function indicators of LOA patients, as pulmonary function is an important evaluation basis for the classification and control of asthma severity."
| PMC
sparser
"QPCR analysis also showed thatMll2 Gdf9 cKO oocytes overexpressed several apoptosis-associated genes ( xref ), including p53 (transformation related protein 53; TRP53) and Setd7 (SET domain lysine methyltransferase 7, also know as Set7/9 ) ( xref and xref ), which methylates p53 and prevents its degradation xref ."
sparser
"Our study suggested that: firstly, healthy controls were more likely to have higher levels of vitamin B 2 and B 12 than ESCC cases; secondly, variant genotype TT and the T allele were associated with significantly increased risk of EPL; thirdly, the MTHFR C677T genotype may modify association between serum vitamin B 2 or B 12 levels and the risks of EPL and ESCC; fourthly, gene–gene interaction was observed as there were strong association between the interaction of p16 and p53 methylations and MTHFR C677T polymorphism and the risks of EPL and ESCC."
sparser
"These results disfavour a role for JMJD3 in the regulation of p53 C-terminal methylation, however, we cannot rule out that JMJD3 is involved in regulating p53 methylation at other lysine residues than the tested ones, or that additional co-factors are required for an efficient enzymatic removal of methylation."