IndraLab
Statements
TP53 activates apoptotic process. 1000 / 16629
|
303
15731
53
reach
"In response to stress, the declining fidelity with age of p53 mediated apoptosis, senescence, and presumably autophagy [XREF_BIBR], suggests that cell injury is accumulated not only due to less DNA repairs but also by reason of the less efficient removal of damaged protein, DNA and organelles in older individuals."
reach
"Of note, the analyses indicated that 33% of the genes involved in p53 pathway and its regulation, and 7% of the genes involved in apoptosis were identified suggesting that the cell killing by i-Extract involves growth arrest or apoptosis, mediated by activation of tumor suppressor p53 pathway."
reach
"XREF_BIBR Paricalcitol prevented cisplatin induced kidney injury by suppressing fibrotic, apoptotic, and proliferative factors in an animal model; paricalcitol suppressed expression of TGF-beta1, Smad signaling, mitogen activated protein kinase signaling, p53 induced apoptosis, and p27 (kip1)."
reach
"Examples of this class include : BAD (BCL-2 antagonist of cell death), BID (BH3 interacting-domain death agonist), BIK (BCL-2 interacting killer), BIM (BCL-2 interacting mediator of cell death), BMF (BCL-2 modifying factor), Hrk (Harakiri), Noxa, and PUMA (p53 up-regulated mediator of apoptosis)."
reach
"In addition, studies have demonstrated that TIGAR also suppresses p53 mediated apoptosis, and that this is in part a result of the enzymatic activity of TIGAR as a fructose-2,6-bisphosphatase which results in a reduction in ROS production with one mechanism being the increased PPP flux and increased production of cellular reducing agents [XREF_BIBR, XREF_BIBR]."
reach
"However, since the authors noticed the enlargement of the endoplasmic reticulum, upregulation of CCAAT-enhancer-binding proteins homologous (CHOP), and p53 upregulated modulator of apoptosis (PUMA) proteins, they suggested that cell death is necroptosis rather than apoptosis [XREF_BIBR]."
reach
"In this context, the effect of autophagy on death sensitivity is not attributable to decreased activity of the TRAIL death effector pathway (including the TNF receptor or the BH3 interacting domain death agonist, BID), but rather to decreased basal expression of the pro death BH3 protein BCL2 binding component 3 (BBC3), also known as p53 upregulated modulator of apoptosis (PUMA)."
reach
"PARP1 is the most abundantly expressed member of the PARP protein family and has been extensively studied in cancer, including DNA damage detection and repair, telomerase protection, chromatin modification, transcriptional regulation, p53 mediated apoptosis, and programmed necrosis."
reach
"Accordingly, BON cells which are TP53 mutated [16,107] showed a relative low induction of primarily p53-driven intrinsic (mitochondrial) apoptosis and the major treatment effect of bortezomib in the analyzed NEN cell lines was induced by extrinsic apoptotic pathways.Current data suggest that PRRT might be effective in the approximately 20% to 30% SSTR2-positive G3 NETs [108], which is currently discussed as therapeutic option for SSTR imaging-positive tumors [109,110]."
reach
"During cellular stress, the p53 tumor suppressor protein blocks cell cycle progression allowing time to repair the damage XREF_BIBR, XREF_BIBR or induces apoptosis largely through the upregulation of the Bcl-2 family BH3-only protein Puma (p53 upregulated modulator of apoptosis) XREF_BIBR - XREF_BIBR."
reach
"Incubation of human lung adenocarcinoma A549 cells with 25 microM Gefitinib resulted in phosphorylation and activation of p53 such as enhanced DNA binding activity, which was accompanied by the upregulation of PUMA (p53 upregulated modulator of apoptosis) and Fas, and downregulation of survivin and XIAP (X linked inhibitor of apoptosis protein)."
reach
"This protein also has other important functions in the regulation of immune response or response to stress factors [XREF_BIBR], and some studies have described its role as a paracrine mediator in the p53 cell signaling pathway that can inhibit cell proliferation and induce apoptosis [XREF_BIBR, XREF_BIBR]."
eidos
"These include multiple layers of transcriptional control , each of which is posited to be activated upon reaching a particular stress threshold , among them the NRF2 pathway , the AP-1 and NF-kB pathways , and , finally , TP53 , which triggers apoptosis if extreme toxicity is reached ."
reach
"This was performed on the intergenic sequence of the Growth arrest specific protein 2 (GAS2) gene, an activator of p53 mediated apoptosis XREF_BIBR, XREF_BIBR, as well as the kallikrein 5 (KLK-5) gene, a secreted protease involved in cancer progression XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR."
reach
"To further elucidate the molecular mechanisms by which IBV induces apoptosis, especially the potential requirement of p53 in IBV induced apoptosis, both p53-null H1299 cells and wild-type p53 containing Vero cells were infected with IBV, and the extent of genomic DNA fragmentation, i.e. the occurrence of the characteristic nuclear hypodiploid DNA content, was analyzed by FACS."
reach
"Our results indicate for the first time that KGF-1 can provide radioprotection to SG epithelial cells by reducing DNA damage and p53 mediated apoptosis following irradiation, in which phosphoinositide 3-kinase (PI3K) - protein kinase B (Akt)-p53 pathway mediates the radioprotective effect of KGF-1."
reach
"This integrated analysis also identified a number of GO terms clustered into programmed cell death and cytoskeleton organization, consistent with the previously reported interactions between CHD8 and p53 mediated apoptosis [XREF_BIBR] and the Wnt-beta-catenin signaling pathway [XREF_BIBR]."
reach
"Our results also demonstrated that phosphorylation of the DNA damage response (DDR) proteins, ATM, Chk1, Chk2 and p53, was inactivated in the LMP1 induced CD44 (+/High) cells in response to DNA damage, and this was accompanied by a downregulation of the p53 targeted proapoptotic genes, which suggested that the inactivation of the p53 mediated apoptosis pathway was responsible for the radioresistance in the CD44 (+/High) cells."
reach
"Phase 1/II clinical trials are ongoing investigating small molecule inhibitors APR-246 (eprenetapopt binds to p53 at two cysteine residues in the DNA binding domain and stabilizes mutant p53), PRIMA-1 (p53 reactivation and induction of apoptosis) and MDM2 inhibitor AMG 232 that restores p53 tumor suppression by blocking the MDM2-p53 interaction [XREF_BIBR]."
reach
"Free fatty acid-induced steatosis was relieved and nonalcoholic steatohepatitis (NASH)-related mechanisms were inhibited in HepG2 cells treated with 30% ethanolic extract of A. capillaris, including activation of c-Jun NH2 terminal kinase (JNK) and p53-upregulated modulator of apoptosis (PUMA) [34]."
| PMC
reach
"Levels of p53 expression, which regulates both proliferation and apoptosis, and caspase-3 expression, an indicator of apoptosis, were significantly induced with continuous and one week on/one week off dosing regimens of aspirin and naproxen, indicating colonic tumor cell apoptosis as part of tumor cell elimination."
reach
"MOs appear to have non-target-related phenotypes including overall developmental delay and cell death due to activation of p53 mediated apoptosis, which can be overcome by using stage matched (rather than age matched) control embryos and co-injection of an anti-p53 MO along with the experimental MO.."
reach
"(2) It is well established that DDX3X participates in transcription and translation of a subgroup of genes that encode cell cycle regulators, including cyclin E1 in HeLa cells XREF_BIBR, cyclin B in yeast XREF_BIBR, cyclin A and cyclin B in hamster cell line ET24 XREF_BIBR; once Ddx3x is knocked down, these cell cycle related proteins potentially decrease and lead to cell cycle arrest and finally activate p53 induced apoptosis."
reach
"Functional polymorphisms in XPD (Asp312Asn, rs1799793 and Lys751Gln, rs1052559), a protein required for nucleotide excision repair and with roles in p53 mediated apoptosis, were modestly associated with G : C --> T : A mutations in TP53 in lung tumors [Asp and Asn312 + Asn and Asn312 and/or Lys and Gln751 + Gln and Gln751 versus Asp and Asp312 + Lys and Lys751; odds ratio (OR) 2.73, 95% confidence interval (CI) 0.98-7.61], consistent with the role of this protein in repair of bulky carcinogen-DNA adducts."
reach
"The thick black line, untreated controls (100%); the blue, yellow, and red dots show differential protein levels after PTX administration for 12, 24, or 48 h, respectively.Fig 12: Expression of downregulated inflammatory proteins (A and B), p53-mediated apoptosis proteins (C and D), and FAS-mediated apoptosis proteins (E and F) in 10 μg/mL PTX-treated RAW 264.7 cells as determined by IP-HPLC."
reach
"Tolfenamic acid reduced mouse double minute 2 (Mdm2), phosphatase and tensin homologue (Pten), P53-upregulated modulator of apoptosis (Puma) and Bcl2-associated X (Bax) at the mRNA level to inhibit apoptosis and downregulated sestrin 2 (Sesn2) and hypoxia inducible factor 1, alpha subunit (Hif-1α) mRNA levels to exert antioxidative stress effects."
reach
"XREF_BIBR We and others showed that, in response to stress, a fraction of induced p53 protein localizes to mitochondria during p-53 mediated apoptosis, where it behaves like a super BH3-only protein to induce mitochondrial outer membrane permeabilization (MOMP), physically interacting with and inhibiting antiapoptotic members (Bcl2, BclxL, Mcl - 1) as well as activating proapoptotic members (Bak, Bax) of the Bcl2 family of MOMP regulators and thereby triggering p53 dependent apoptosis (see below)."
reach
"Indole-3-carbinol suppresses NF-kappaB activity and stimulates the TP53 dependent pathway and its downstream target genes encoding TP53 Upregulated Modulator of Apoptosis (PUMA), Phorbol-12-Myristate-13-Acetate-Induced Protein (PMAIP)-1, and Apoptotic Protease Activating Factor (APAF) -1 in pre-B acute lymphoblastic leukemia cells [XREF_BIBR]."
reach
"XREF_BIBR Remarkably, it is the MDM2 and MDM4 heterodimer that plays a pivotal role in the p53 regulation network; primarily by controlling p53 abundance through proteasomal degradation, and also because of its involvement both in the regulation of p53 transcriptional activity and p53 induced apoptosis."
reach
"A potential limitation to this strategy comes from the observation that p53 reactivation via MDM2-antagonists such as Nutlin-3 not necessarily cause apoptosis in cancer cells, but it may also determine a transient growth inhibition depending on the cell and molecular context, with obvious consequences on its possibility to eradicate cancer."
reach
"Since the deletion of p53 enhances proliferation and inhibits apoptosis, the deletion of p53 may increase cell density in cultures, leading to the acceleration of osteoblast differentiation in vitro because osteoblast differentiation is dependent on cell density in vitro [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
reach
"The original model supported the notion that p19 Arf induction antagonizes Mdm2, the negative regulator of p53; the stabilized p53 promotes the progression of a transcriptional program that, ultimately, arrests cell proliferation, facilitates DNA damage responses, or promotes apoptosis."
reach
"We did not find a statistically significant association between the investigated polymorphisms and development of CZS; however, by comparing individuals with CZS and lissencephaly or without lissencephaly, we found a significative difference in the allelic frequencies of the TP53 rs1042522, which is associated with a more potent p53-induced apoptosis (p=0.007)."
reach
"XREF_BIBR Changes in the expression of genes involved in cell cycle, especially up-regulation of CDK4 and MDM2, could accelerate cell cycle progression, support cell proliferation, suppress p53 induced apoptosis, and finally facilitate the malignant transformation of adipose cells into DDLPS cells."
reach
"Consistent with these results, LPS induced AKI and renal tubular cells apoptosis were ameliorated by novel potential agents, such as a pluripotent autocrine growth factor progranulin, an anion transporter uncoupling protein 2 [XREF_BIBR], the bee venom [XREF_BIBR], and peroxiredoxin protein DJ-1 (Parkinson disease protein 7, Park7) [XREF_BIBR], as well as by vitamin D that suppressed p53 upregulated modulator of apoptosis (PUMA) and upregulated expression of a Bcl-2 family antiapoptotic protein [XREF_BIBR]."
reach
"SIRT1 regulates longevity factors and several factors by deacetylation of Forkhead box (FOXO) family, SIRT1 probably acts via different mechanisms to regulate age related changes including increasing mitochondriogenesis via modulating PGC-1alpha deacetylation, repressing oxidative stress survival response via FOXO family, reducing apoptosis and proliferation caused by p53 deacetylation, and mitigating pro inflammatory response via NF-kappaB activation."
reach
"We demonstrated that AdVING4 and p53 mediated p53 and ING4 co-expression induced synergistic growth inhibition and apoptosis as well as enhanced effects on upregulation of acetylated p53, P21, Bax, PUMA, Noxa, cleaved caspase-9, cleaved caspase-3 and cleaved PARP, and downregulation of Bcl-2, CD31 and microvessel density (MVD) in MDA-MB-231 breast cancer in vitro and/or in vivo subcutaneous (s.c.) xenografted tumors."
reach
"XREF_BIBR Their presumptive mechanism of action is to dissociate bax or bak from antiapoptotic bcl-2 family proteins, allowing them to translocate to the outer mitochondrial membrane to form pores that allow the cytoplasmic release of cytochrome c. XREF_BIBR, XREF_BIBR Of the eight known BH3-only genes, Bid is a critical mediator of apoptosis mediated by death receptor signaling, XREF_BIBR Bim is the determinant of taxane responsiveness, XREF_BIBR Puma and Noxa are central mediators of p53 induced apoptosis, XREF_BIBR and Bad regulates apoptosis mediated by growth factor and cytokine signaling."
reach
"For example, the miR-17-miR-92 cluster in T-cell acute lymphoblastic leukaemia reduces the level of the transcription factor E2F1; miR-21 downregulates the tumour inhibiting factor PTEN in lung cancer cells; and miR-125b is an important repressor of p53 and inhibits p53 induced apoptosis in human neuroblastoma cells."
reach
"Further evidence in favor of the intrinsic apoptotic pathway inhibition by the infection was revealed by the behavior of the proapoptotic mitochondrial proteins of Bcl-2 family, namely : the Bcl-2-associated protein X (Bax); the p53 upregulated modulator of apoptosis (Puma); the pro apoptotic (Bim); the Bcl-2-interacting domain (Bid); and Bad."
reach
"The mRNA and protein levels of three apoptosis related genes (p53 and bax are promoters of apoptosis, whereas bcl-2 is apoptotic suppressor) were analyzed in lungs using a real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) assay and immunohistochemistry method, and caspase-3 activities were detected."
reach
"However, Bennett et al. [XREF_BIBR] found that abrogation of endogenous p53 activity in cultured VSMC from human coronary atherosclerotic plaque did not increase cell proliferation or support apoptosis although plaque VSMC are very sensitive to p53 mediated apoptosis, suggesting that endogenous p53 is not pro apoptotic and over sensitivity to apoptosis of plaque VSMC is not driven by p53."
reach
"By using an in vitro system with cultured t (14; 18)-positive DLBCL cells, or a xenograft lymphoma animal model, our data show that nutlin-3a can activate the p53 pathway inducing cell cycle arrest and apoptosis in t (14; 18)-positive DLBCL cells with wt p53, overcoming BCL2 overexpression."
reach
"It is possible that Apela has multiple modes of action depending on the developmental stages : in mESCs, it regulates p53 mediated apoptosis independent of its coding ability while during early development, it controls cell movement through encoded Apela peptide and the Apela and Aplnr axis."
reach
"This study aims to investigate the role of targeting lncRNA myocardial infarction associated transcript (MIAT) in protection against hypoxia and reoxygenation (H/R) injury in H9c2 cells in vitro and myocardial ischemia and reperfusion (I/R) injury in vivo by regulating expression of NF-kB and p53 upregulated modulator of apoptosis (PUMA)."
reach
"While topoisomerase 2beta (expressed mostly in proliferating cells) is considered as the primary target of DOX in tumor cells, topoisomerase 2alpha (expressed by quiescent cells) has been made responsible for suppression of antioxidant enzyme expression, inhibition of mitochondrial biogenesis, and activation of p53 and p53 mediated apoptosis with all of these cellular events implicated in DOX induced heart failure [XREF_BIBR]."
reach
"Further functional protein association analysis of significantly regulated genes associated with these two synthetic lethal pathways indicated that GSK3 played a key role in p53 mediated A549 cell apoptosis, and then gene function study was performed, which revealed that GSK3 inhibition promoted p53 mediated A549 cell apoptosis in a p53 post-translational activity dependent manner."
reach
"One of the most interesting properties of Nef is its interaction with the p53 tumor suppressing protein via its N-terminus, which destabilizes p53, leading to a decrease in its proapoptotic, transcriptional and DNA binding activities, and indeed protecting HIV infected cells from undergoing p53 mediated apoptosis."
reach
"In addition, we further explored the relevance of p53 in the mechanism of apoptosis elicited by IQ3A, by silencing KRAS in HCT116 p53 wild-type (p53 (+/+)) and null (p53 (-/-)) isogenic cell lines, and evaluating its impact on cell death, and on IQ3A induced cell death (XREF_FIG)."
reach
"Likewise, following in utero AzaD exposure, striking upregulation of genes encoding a number of pro apoptotic factors (e.g. Fas, Tnf, Tnfrsf10b, Tp53, Bax, Apaf1, Myc and Nfkb2, among others) is also consistent with the observed activation of various apoptosis inducing canonical cascades (e.g. Apoptosis-, Death receptor-, Myc mediated apoptosis-, and p53 mediated apoptosis signaling pathways; XREF_SUPPLEMENTARY)."
reach
"An advantage of this approach is that the compounds identified e.g., nutlin, RITA (Reactivation of p53 and induction of tumor cell apoptosis) and PRIMA-1 (p53 reactivation and induction of massive apoptosis) have a desired biological outcome such as apoptosis and rarely display genotoxicity [XREF_BIBR - XREF_BIBR]."
reach
"Although wild type p53 is well recognized to induce apoptosis, which is also supported by our data, we found that apoptosis was suppressed by RAS and ERK, but promoted by RAS and AKT in the selected ovarian cancer cell model, which are inconsistent with previous reports XREF_BIBR, XREF_BIBR."
reach
"The PVDF membranes were incubated by primary antibodies at a dilution of 1:500 or 1:1000 to detect procaspase-9, caspase-9, procaspase-3, caspase-3 (Cell Signalling), COX3, GAPDH (Santa Cruz), collagen I, collagen III, BAX, BAK, Bcl-2, Bcl-xL, Bcl-2-associated death promoter (BAD), p53 upregulated modulator of apoptosis (PUMA), beta-actin, Apaf-1, Cyt c, EndoG, AIF (GeneTex) and alpha-SMA (abcam)."
reach
"Although an overall increase of acetylated p53 in CITED2 deficient cells was detected, treatment of cells with the CBP and p300 inhibitor C646 as well as RNAi mediated knockdown of CBP and P300 could not rescue the effect on p53 mediated apoptosis and target gene expression, indicating that p53 activation upon CITED2 knockdown is not due to increased activity of CBP and p300 towards p53."
reach
"Mechanistically, the inhibition of p53 prevented the cardiac apoptosis during early-stage diabetes (0.5 month), attenuated diabetes induced cell senescence (3 and 6 months), and improved both glycolytic and angiogenic defects by increasing hypoxia induced factor (HIF)-1alpha protein stability and upregulating HIF-1alpha transcription of specific target genes at 3 and 6 months after diabetes."
reach
"PMUA, (p53 Upregulated modulator of apoptosis) (PUMA), a Bcl-2 homology 3 (BH3)-only Bcl-2 family member, plays an essential role in p53 dependent and -independent cell apoptosis induced by a variety of stimuli, including inhibitedde regulated oncogene expression, genotoxic stress, growth factor and cytokine withdrawal and infection, toxins, altered redox status XREF_BIBR - XREF_BIBR."
reach
"Another observation was that, while LBH589-treatment was associated with the induction of ER stress- and apoptosis-related genes in IPF-fibroblasts, as shown by increases in ATF6- (activating transcription factor-6, Fig 3I), CHOP- (C/EBP homologous protein, Fig 3J), DR5- (death receptor 5, Fig 3K), PUMA- (p53 upregulated modulator of apoptosis, Fig 3L) and CIP1/p21 transcripts (Fig 3M), treatment with pirfenidone did not elicit this kind of response."
reach
"Indeed, p53’s ability to induce apoptosis in aberrant cells was exploited in clinical trials in the late 1990s, but the therapy failed due to the DN effect, inability to overcome other mutated oncogenes, immunogenic issues with adenoviral delivery, and inefficient targeting of cancer cells [9]."
reach
"Leker et al. have reporetd that, although p53 has a short half-life and its activity maintains at low level under no stress, resident p53 translocation into nuclei and binding to its specific DNA sites are early events in p53-induced apoptosis in neurons following ischemic insults."
reach
"The Akt-mTORC2 signaling plays a critical role in survivalbility of cells under stressful conditions such as : (i) activation of PKCalpha that maintains microtubule integrity (cytoskeletal dynamics) (ii) controlling ion transport and cellular growth via serine/threonine protein kinase (SGK1) phosphorylation (iii) inhibiting PKR mediated inflammatory response and upregulation of interferons (iv) interfering caspase protein and p53 mediated apoptosis and (iv) inhibition of MNK1 that shutoff both cap dependent and cap independent translation."
reach
"Ovarian accumulation of galactose and galactose-1-phosphate may exert direct apoptotic effects, while the extra-ovarian effect of galactose may involve attenuation of FSH bioactivity followed by withdrawal of protection from ROS insult and activation of p53 mediated granulosa cell apoptosis."
reach
"However, because Apaf-1, caspase-9 and cytochrome c form apoptosome in the presence of dATP, which activates the postmitochondrial mediated caspase cascade, resulting in apoptosis, another factor needed for the enhancement of p53 inducing apoptosis by co-induction of Apaf-1 and caspase-9 might be several mitochondrial proteins that are induced by p53 as the direct-targets, such as Noxa and Puma (Oda et al, 2000; Nakano and Wousden, 2001)."
reach
"In particular, our results show that (i) loss of K117 acetylation on mouse p53 (corresponding to K120 of human p53) specifically abrogates transactivation of proapoptotic p53 gene targets; (ii) p53 K117R is defective for p53 mediated apoptosis, but retains the cell cycle arrest and senescence functions of p53; (iii) unlike p53-null mice, p53 K117R and K117R animals do not develop early-onset tumors, suggesting that apoptosis is largely dispensable for p53 mediated tumor suppression, at least in this biological setting; (iv) loss of acetylation at three sites (p53 3KR : K117, K161, and K162) in the DNA binding domain of mouse p53 abrogates p53 mediated cell cycle arrest, apoptosis, and senescence, (v) p53 3KR mice do not develop early-onset tumors, indicating that p53 dependent cell cycle arrest, apoptosis, and senescence are not absolutely required for p53 tumor suppression; and (vi) p53 3KR retains the ability to modulate energy metabolism and reduce reactive oxygen species (ROS) by regulating metabolic p53 target genes in vivo."
reach
"However, the expression of Puma, Noxa, and p21 was not abrogated in these mutants, only reduced; therefore, the possibility that the reduced levels of these critical effectors of p53 mediated apoptosis and G1/S-cell-cycle arrest sufficed to prevent tumorigenesis could not be excluded."
reach
"Western blot and qPCR analyses showed that LAMB3 overexpression upregulated cyclin D1, which promoted cell cycle progression, and BCL-2, which inhibited apoptosis, and downregulated p53, which arrested cell cycle progression and promoted apoptosis; the LAMB3 knockdown group had the opposite effect."
reach
"However, during the later stages, CHK2 may contribute to p53 phosphorylation at Ser366 and Ser378, resulting in p53 degradation through the ubiquitin-proteasome pathway and blocking of p53 mediated apoptosis [XREF_BIBR] and the EBV protein kinase BGLF4 contributes to p27 phosphorylation and its ubiquitin-proteasome dependent degradation [XREF_BIBR]."
reach
"According to a study on the roles of p53 to induce Cer accumulation by the activation of sphingomyelinases XREF_BIBR, it may be explained that the conversion of SM to Cer did not effectively progress in hypothalamus, resulting in the accumulation of SMs due to the inhibition of apoptosis caused by p53 deficiency."
reach
"Additionally, the observation of mitochondrial membrane potential loss along with caspases activation and generation of ROS may support the hypothesis that p53 (either wild type or mutant) may have induced apoptosis via the mitochondrial pathway through transcription-independent mechanisms."
reach
"[XREF_BIBR, XREF_BIBR] Following gamma irradiation, the p53 mediated apoptosis mechanism in Per2 deficient mice does not function adequately [XREF_BIBR] and as a result, c-Myc expression is not downregulated and the damaged cells are capable of bypassing the cell cycle checkpoints regardless of the presence of DNA damage, increasing the risk for neoplastic transformation."
reach
"In this study, we found that mice harboring a hypomorphic mutant p53, R172P, a mutation that abrogates p53 mediated apoptosis while keeping cell cycle control mostly intact, are more susceptible to ultraviolet-B (UVB)-induced skin damage, inflammation and immunosuppression than wild-type mice."
reach
"However, this gene is inactivated by mutation in half of all human cancers.31 Most of the TP53 mutations are missense mutations, resulting in amino acid substitutions in the DNA binding core domain, and TP53 mutations disrupt p53 specific DNA binding and transcriptional transactivation, leading to the loss of functions as a tumor suppressor.32 The small molecule PRIMA-1 has been identified in the low molecular weight compound library to restore mutant p53 to the structure and function of wild-type p53 by targeting the p53 DNA binding core domain, resulting in the induction of p53 mediated apoptosis.24, 33 However, the mechanisms underlying how PRIMA-1 induces apoptosis in TP53 mutant cancer cells to change the conformation of p53 mutant protein have not been fully understood."
reach
"Given that p53 functions as a transcriptional activator, with transcriptional targets playing critical roles in p53 induced apoptosis, we also examined the potential transcriptional p53 downstream targets PUMA, Apaf1, Bax, and Bcl-2, all known to be involved in apoptosis regulation."
reach
"RAW 264.7 cells treated with AC-5 or AC-10 showed slight increases in the expression of BAD (109.3%), APAF-1 (108.2%), c-caspase 9 (102.4%), and c-caspase 3 (103.5%), suggesting a slight activation of p53-mediated apoptosis but otherwise no significant changes in the expression of p53-mediated apoptosis-related proteins (Fig. 4C2)."
reach
"For the functioning of p53 as a tumor suppressor, wild-type p53 activates the transcription of its downstream genes such as p21 WAF1 and Bax to inhibit cell proliferation and induce apoptotic process in DNA damaged cells or cancer cells [XREF_BIBR - XREF_BIBR] where as the malfunctioning of wild-type p53 attenuates its normal function in cancer."
reach
"Thus, a p53 stabilization would, at a first glance, induce cell cycle arrest, senescence and/or increase in apoptosis, which is not in line with Hoxa2 functional studies that led to postulate anti-differentiation and pro proliferative roles for Hoxa2 [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
reach
"On the other hand, HRas signalling reaches the nucleus via phosphorylation of c-Jun N-terminal kinases (JNKs) [XREF_BIBR, XREF_BIBR], which in turn is able to stabilize p53 by hindering mouse double minute 2 homolog (MDM2) binding, increasing p53 activation and supporting p53 induced apoptosis [XREF_BIBR]."
reach
"Interestingly, ferroptotic agent also induces ER stress through the UPR and activates ER stress-related response genes such as DR5 (death receptor 5), PUMA (p53 upregulated modulator of apoptosis), ATF4 (activating transcription factor 4), and CHOP (C/EBP (CCAAT‐enhancer‐binding protein)‐homologous protein) [Dixon et al., 2014; Lee et al., 2019; Ohoka et al., 2005; Rahmani et al., 2007; Su and Kilberg, 2008]."
reach
"Ribosomal stress and Tp53- mediated neuronal apoptosis in response to capsid protein of the Zika virus OPEN.We report here that in rat and human neuroprogenitor cells as well as rat embryonic cortical neurons Zika virus (ZIKV) infection leads to ribosomal stress that is characterized by structural disruption of the nucleolus."
reach
"MUC1 can also be involved protein p53 transcription regulation after genotoxic stress, inhibiting p53-mediated apoptosis and promoting cell cycle arrest (24), therefore MUC1 can block cell cycle and proliferation in osteoblasts cells.In addition, MUC1 also activates IκB (Kinase beta complex) (25) therefore releasing IκBα activating NF-κB p65/RelA (26), so contributes to the activation of canonical NF-κB pathway (27)."
reach
"While siRNA mediated knockdown of DKK3 in H460 lung cancer cells has been recently shown to cause apoptosis and increased levels of p53, p21 CIP1 and BAX XREF_BIBR, we demonstrate that DKK3-shRNA mediated knockdown had no effect on phospho-p53 and BAX levels but increased p27 KIP1 and reduced p21 CIP1 levels."
reach
"Because p53 mediates apoptosis through the intrinsic mitochondrial pathway, 40 which in turn is affected by total and mitochondrial reactive oxygen species (ROS), 41 we wondered whether HTS 's effect on proliferation and the double-treatment effect on apoptosis were mediated by alterations of cellular and mitochondrial redox level and mitochondrial activity."
reach
"As early as 2004, Obach et al. [XREF_BIBR] provided evidence that other proteins could transactivate at least PFKFB3, and indeed other such mediators have been identified, including TP53 induced regulator of glycolysis and apoptosis (TIGAR), although in this case the effect is a down-regulation [XREF_BIBR]; IL-3 [XREF_BIBR]; and progestin [XREF_BIBR]."
reach
"Knockdown of individual subunits of CK2 demonstrated a differential decrease of gene expression of not only NF-kappaB but also cell survival (BCL-XL) and cell cycle progression (CCND1) genes, whereas an increase of TP53 family genes known to promote growth arrest and apoptosis (p53 and Tap63) was observed."
reach
"In the last group, one can further distinguish between activators (Bcl-2-interacting mediator of cell death (Bim) and Bcl-2-interacting domain death agonist (Bid)) and sensitisers (e.g., p53 upregulated modulator of apoptosis (Puma), Bcl-2-associated death promoter (Bad), Noxa, Bcl-2-interacting killer (Bik) and more)."
reach
"The last group is called BH3-only proteins and contains BCL2 interacting mediator of cell death (BIM), p53 upregulated modulator of apoptosis (PUMA), BH3 interacting-domain death agonist (BID), BCL2 associated death promoter (BAD), Phorbol-12-myristate-13-acetate-induced protein 1 (NOXA), BCL2 interacting killer (BIK), BCL2 modifying factor (BMF) and activator of apoptosis harakiri (HRK) proteins."
reach
"In addition, a recent study demonstrated that sunitinib induces the p53 upregulated modulator of apoptosis (PUMA), which plays an essential role in p53 dependent and -independent apoptosis in human cancer cells and mice, but its expression is independent of p53 in colon cancer cells."
reach
"While p53 activation results in p53 dependent programmed cell death (apoptosis) in many cell types, melanocytes are resistant to UV induced apoptosis suggesting that p53 activity is somehow blocked (non functional p53), a state shared with melanoma cells that are resistant to conventional modes of chemotherapy that aim to stimulate p53 dependent apoptosis."
reach
"HMGA1 has been shown to decrease cellular apoptotic pathways by : (1) preventing the p53 mediated apoptosis by translocating the HIPK2, a p53 proapoptotic activator, from nucleus to cytoplasm; (2) inhibiting transcriptional suppression of the anti-apoptotic gene Bcl-2; (3) decreasing the expression of the Bcl-2-specific miR-34; and (4) regulating the p53 expression by suppressing its promoter activity."
reach
"In the present study, the levels of antiapoptotic proteins BCL2 and BCLX were upregulated in response to BeWo cells treated with NOB (100 μM) for 48 h, which suggested that NOB attenuated apoptosis by blocking a step which was critical for the activation of caspases.The p53 tumor suppressor gene is a transcription factor that mediates apoptosis by activating the mitochondrial pathway in a hypoxic environment [36]."
eidos
"Only four unique biological pathways were positively enriched in the NUCL group , including `` Initiation of Nuclear Envelope Reformation '' , `` Nuclear Envelope Reassembly '' during mitotic cell cycle `` 45 , '' apoptosis induction by P53 `` 46 '' and actin dynamic during phagocytosis `` 47 ."
| PMC
reach
"In order to modulate infected cell factors, Kaushansky and colleagues [XREF_BIBR, XREF_BIBR] revealed that pharmacological interventions to increase levels of p53 (Nutlin-3) and block BCL-2 family activities (ABT-737 or Obatoclax) selectively lead to mitochondrial apoptosis of P. yoelii infected hepatocytes, reducing liver stage burden and cell susceptibility to sporozoite infection."
reach
"Furthermore, HIF1alpha appears to enhance p53 activation by ionizing radiation (IR), resulting in increased p53 phosphorylation and p53 mediated apoptosis 123 IR significantly increases HIF1alpha activity in tumors due to increased reactive oxygen and nitrogen species, and rad iation combined with hypoxia lead to increased p53 phosphorylation in a HIF1alpha dependent manner, by a mechanism that rema ins unclear."