Tumor protein p53 is a nuclear transcription factor that regulates the expression of a wide variety of genes involved in apoptosis, growth arrest, or senescence in response to genotoxic or cellular stress One of the most important p53 functions is its ability to activate apoptosis, and disruption of this process can promote tumor progression and chemoresistance. p53 apparently promotes apoptosis.. P53 induces apoptosis in nontransformed cells mostly by direct transcriptional activation of the pro-apoptotic BH3-only proteins PUMA and (to a lesser extent) NOXA. Combined loss of the p53.. p53 upregulated modulator of apoptosis. The p53 upregulated modulator of apoptosis (PUMA) also known as Bcl-2-binding component 3 (BBC3), is a pro- apoptotic protein, member of the Bcl-2 protein family. In humans, the Bcl-2-binding component 3 protein is encoded by the BBC3 gene. The expression of PUMA is regulated by the tumor suppressor p53 Using the p53 inhibitor, pifithrin-α (PFT-α), and RNA interference (RNAi) directed at p53, we demonstrate that p53 function and expression are required for CSE-mediated apoptosis. The expression of macrophage migration inhibitory factor (MIF), an antiapoptotic cytokine produced by HPAECs, also increases in response to CSE exposure
Das p53-Protein spielt eine zentrale Rolle bei der Expression von Genen, die an der Regulierung der Apoptose und der DNA-Reparatur beteiligt sind. Im Jahre 1992 wurde ihm der Name Wächter des Genoms (Lane, 1992) verliehen. 1993 wurde es zum Molekül des Jahres gekürt Der humane Tumorsuppressor p53 reguliert als Transkriptionsfaktor nach DNA-Schädigung die Expression von Genen, die an der Kontrolle des Zellzyklus, an der Induktion der Apoptose (des programmierten Zelltods) oder an der DNA-Reparatur beteiligt sind. Aufgrund dieser Eigenschaft wird p53 in der Literatur als Wächter des Genoms bezeichnet Dieser Weg kann ausgelöst werden durch Tumor-Suppressoren, wie beispielsweise p53, einem Transkriptionsfaktor, der durch Schädigung der DNA aktiviert wird. p53 stimuliert die Expression pro-apoptotisch wirkender Mitglieder der Bcl-2 Familie (z. B. Bax, Bad). Diese führen dann zur Freisetzung der pro-apoptotischen Faktoren - wie etwa Cytochrom c - aus dem mitochondrialen Intermembranraum. Jedoch wirken viele toxische Substanzen, wie z. B. Chemotherapeutika, auch direkt auf.
The ability of p53 to eliminate excess, damaged or infected cells by apoptosis (Kerr et al., 1972) is vital for the proper regulation of cell proliferation in multi-cellular organisms (Huang and Strasser, 2000). p53 is activated by external and internal stress signals that promote its nuclear accumulation in an active form p53 Is Required for DNA Damaging Drug-induced Apoptosis in SH-SY5Y Cells. Given that p53 is functional in SH-SY5Y cells and the well-known role that p53 plays in regulating apoptosis, we examined the contribution of p53 to DNA damaging drug-induced apoptosis in SH-SY5Y cells by abrogating endogenous p53 activity p53 is a major tumor suppressor that kills by apoptosis. The prominent anticancer drug 5-fluorouracil (5-FU) kills cells selectively through the p53 pathway (16). Cells lacking IP6K2 display profoundly reduced 5-FU-mediated apoptosis with markedly decreased cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-3 (Fig. 2A)
When p53 was returned to the wild-type conformation, E1A+p53 transformants underwent cell death by apoptosis. This induction of apoptosis by conformational shift of p53 from the mutant to the wild-type form was inhibited by expression of the E1B 19K protein. Thus, the p53 protein may function as a tumor suppressor by initiating a cell suicide response to deregulation of growth control by E1A. The response was mediated by p53 and the ATM (ataxia telangiectasia mutated) kinase, consistent with activation of a DNA damage checkpoint. Apoptosis was not due to rupture of dicentric chromosomes.. The p53 gene encodes a transcription factor that can regulate cell proliferation and survival by modulating transcription of downstream target genes, inducing either G 1 arrest or apoptosis (1, 10-13). p53 is activated to promote G 1 arrest or apoptosis by several stimuli, the most well characterized being DNA damage. Many known anticancer agents cause DNA damage, presumably leading to p53-dependent apoptosis. Inactivation of the apoptotic response provides an attractive. P53, Apoptosis, and Breast Cancer Diana M. Barnes l~ and Richard S. Camplejohn 2 Wild-type p53 is a tumor suppressor gene that plays a central role in maintaining the genetic integrity of the cell by preventing cells with damaged DNA from further proliferation. Mutation and deletion of p53 are the most common genetic defects seen in clinical cancer. About 40%.
Transcription-independent p53-induced apoptosis is important in the shear-stimulated Mk-particle generation and the biological effectiveness of these particles. To determine the importance of shear-stimulated TIPA on Mk maturation, we examined how modulating its activity affected the biogenesis of Mk particles (PPTs, PLPs, and MkMPs) from day 12 Mks. Our lab has previously shown that shear. P53 was the first tumor suppressor gene linked to apoptosis. Mutations in this tumor suppressor gene occur in the majority of human tumors and are often associated with advanced tumor stage and poor patient prognosis. Studies using p53 knockout mice demonstrated that endogenous p53 could participate in apoptosis The tumor suppressor p53 exerts its anti-neoplastic activity primarily through the induction of apoptosis. We found that cytosolic localization of endogenous wild-type or trans-activation-deficient p53 was necessary and sufficient for apoptosis. p53 directly activated the proapoptotic Bcl-2protein Bax in the absence of other proteins to permeabilize mitochondria and engage the apoptotic. Pifithrin-μ (NSC 303580, PFTμ, 2-Phenylethynesulfonamide) is a specific p53 inhibitor by reducing its affinity to Bcl-xL and Bcl-2, and also inhibits HSP70 function and autophagy. Effect of pifithrin-μ (the inhibitor of mitochondrial translocation of p53) on MEG3-induced apoptosis in TGF-β1-treated LX-2 cells
Using the p53 inhibitor, pifithrin-α (PFT-α), and RNA interference (RNAi) directed at p53, we demonstrate that p53 function and expression are required for CSE-mediated apoptosis. The expression of macrophage migration inhibitory factor (MIF), an antiapoptotic cytokine produced by HPAECs, also increases in response to CSE exposure. The addition of recombinant human MIF prevents cell death. Introduction. MDM2 is a ubiquitin E3 ligase for p53 and an important regulator of p53 stability and activity by forming a negative feedback loop ( 1, 2).Overexpression of MDM2 abrogates the ability of p53 to induce cell cycle arrest and apoptosis ( 3).In ∼30% of human osteogenic sarcomas and soft tissue sarcomas, MDM2 is overexpressed due to gene amplification The p53-Mediated Apoptosis Cocktail is designed to study the induction of p53-mediated apoptosis in response to various stimuli. The two main components of this cocktail are monoclonal antibodies specific to PARP (cleaved) and p53 (phosphorylated at serine 46). The GAPDH antibody is provided as a loading control for sample to sample normalization. Since the primary antibodies are both mouse.
Slug antagonizes p53-mediated apoptosis of hematopoietic progenitors by repressing puma. Wu WS(1), Heinrichs S, Xu D, Garrison SP, Zambetti GP, Adams JM, Look AT. Author information: (1)Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. Comment in Cell. 2005 Nov 18;123(4):545-8. In response to DNA damage, the p53 tumor. Introduction. The p53 tumor suppressor protein is stabilized and activated by a variety of cellular stresses such as heat shock, hypoxia, osmotic shock, and DNA damage, which in turn leads to growth arrest and/or apoptosis (25, 13, 15 for review).However, it is still largely unknown how p53 selects the pathways of G1-arrest or apoptosis As mentioned previously, p53 then signals growth arrest of the cell at a checkpoint to allow for DNA damage repair or can cause the cell to undergo apoptosis if the damage cannot be repaired. This system can also be inactivated by a number of mechanisms including somatic genetic/epigenetic alterations and expression of oncogenic viral proteins such as the HPV, leading to tumorigenesis (Bolt et. Home > Life Science Research > Products > PCR Amplification > PrimePCR™ PCR Primers, Assays, and Arrays > PrimePCR Pathways > Transcription factors > Apoptosis and survival - p53-dependent apoptosis SIRT1 deacetylates p53 and suppresses p53-mediated transcriptional activity, thereby reducing the expression of its downstream molecules involved in cell cycle arrest and apoptosis. Thus, SIRT1.
p53-dependent apoptosis is essential for the antitumor effect of paclitaxel response to DNA damage in papillary thyroid carcinoma . Wenshuang Wu 1,2*, Tao Wei 1*, ZhiHui Li 1,2, Jingqiang Zhu 1 . 1. Department of Thyroid Surgery, West China Hospital, Sichuan University, Chengdu, China 2. Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular. Role of p53 in apoptosis induced by PHD (prolyl hydroxylase domain) inhibition using CoCl 2 in cultured rat cardiomyocytes. A, Tp53 expression in cultured cardiomyocytes, treated with vehicle (Veh) and CoCl 2 (500 μmol/L) for 24 hours, or transfected with small interfering RNA (siRNA) for control (CTL) (scramble siRNA, CTL) and p53, was quantified by quantitative reverse transcription. Keywords p53 Apoptosis Proliferation Growth Drosophila Introduction The p53 protein is the product of the tumor suppressor gene, TP53. It is a member of the p53 superfamily proteins that comprise TP53, TP63 and TP73. p53 is mutated or inactivated in more than half of human cancers. Early works on p53 have elucidated its canonical function in response to DNA damage. Specifically, in the.
P53 is a key transcription factorthat regulates the expression of genes involved in apoptosis and cell cycle arrest , , . In the cytosol p53 binds to mdm2 and is rapidly degraded. Hence, the half life of p53 is short (less than 30 minutes) and constitutive expression of p53 is barely detectable in lymphocytes using conventional western blotting method. Acetylation of lysine residues on p53. p53 has seven domains: . an acidic N-terminus transcription-activation domain (TAD), also known as activation domain 1 (AD1), which activates transcription factors.The N-terminus contains two complementary transcriptional activation domains, with a major one at residues 1-42 and a minor one at residues 55-75, specifically involved in the regulation of several pro-apoptotic genes Inositol pyrophosphates have been implicated in numerous biological processes. Inositol hexakisphosphate kinase-2 (IP6K2), which generates the inositol pyrophosphate, diphosphoinositol pentakisphosphate (IP7), influences apoptotic cell death. The tumor suppressor p53 responds to genotoxic stress by engaging a transcriptional program leading to cell-cycle arrest or apoptosis p53 and Apoptosis: It's Not Just p53include genesimplicated inmediating growtharrest in the Nucleus Anymore as well as genes that encode proteins involved in regu-lating apoptosis (reviewed in Vousden and Lu, 2002). Tumor-derived mutant p53 proteins exhibit defects in the ability to bind DNA and therefore to affect gene The tumor suppressor p53 triggers apoptosis in re- expression, arguing.
The tumor suppressor p53 has established functions in cancer. Specifically, it has been shown to cause cell-cycle arrest and apoptosis in response to DNA damage. It is also one of the most commonly mutated or silenced genes in cancer and for this reason has been extensively studied. Recently, the role of p53 has been shown to go beyond its effects on cell cycle and apoptosis, with effects on. The tumor suppressor p53 triggers apoptosis in response to a variety of stress stimuli. Its role as a transcription factor modulating gene expression has been clearly implicated in this process. Two recent publications now argue for an additional direct role of p53 at the mitochondria in inducing apoptosis Low levels of p53 protein and chromatin silencing of p53 target genes repress apoptosis in Drosophila endocycling cells; Structure of the apoptosome: mechanistic insights into activation of an initiator caspase from Drosophila; Dying cells protect survivors from radiation-induced cell death in Drosophila; Tie-mediated signal from apoptotic cells protects stem cells in Drosophila melanogaster.
KEGG analysis based on transcriptome profiling indicated that p53 signaling and apoptosis are the only observed pathways in AFB 1-treated embryos. AFB 1 at 0.5 μM significantly activated the expression of tp53, mdm2, puma, noxa, pidd1, and gadd45aa genes that are related to the p53 pathway and also that of baxa, casp 8 and casp 3a in the apoptotic process. TUNEL staining demonstrated that AFB. p53-dependent apoptosis is hypothesized to help preserve genome stability by rapidly eliminating cells with severe chromosome damage. In mouse models with elevated genomic instability, loss of p53 function further increases tumorigenesis (A ttardi 2005). However, temporal analysis of mouse p53 function following irradiation suggests that the DNA damage response function of p53 may not be. Recent evidence suggests transcription-independent p53 apoptosis pathways in which p53 translocates to the mitochondria, interacts with Bcl-XL, induces PT and the release of cytochrome c [Mihara, 2003]. In non-stressed, undamaged cells p53 therefore must be kept under stringent control: it is present only at low cellular concentrations, it is retained in the cytosol and prevented to enter the. Activation of cAMP signalling potently inhibits DNA damage-induced apoptosis in acute lymphoblastic leukemia cells by promoting the turnover of p53 protein. Recently, we showed that the cAMP-induced destabilization of p53 in DNA-damaged cells occurs as a result of enhanced interaction between p53 and HDM2. In this report, we present results showing that increased levels of cAMP in cells with.
Introduction. The p53 tumor suppressor/transcription factor regulates various cell functions, including the promotion of apoptosis and senescence, and the suppression of cell growth, migration, and invasion ().Most studies of the mechanisms of p53 action have focused on the transcriptional targets of p53, which mediate p53 functions. p21 WAF1 represents one such target, which plays important. p53 acts as a tumor suppressor by inducing both growth arrest and apoptosis. p53-induced apoptosis can occur without new RNA synthesis through an unknown mechanism. In human vascular smooth muscle cells, p53 activation transiently increased surface Fas (CD95) expression by transport from the Golgi complex. Golgi disruption blocked both p53-induced surface Fas expression and apoptosis. p53 also.
http://technologyinscience.blogspot.in/2015/05/p53-structure-and-function-cell-cycle.htmlp53 is a tumor suppressor gene, present in eukaryotic cell. Protein. Apoptosis-stimulating of p53 protein 2 (ASPP2) also known as Bcl2-binding protein (Bbp) and tumor suppressor p53-binding protein 2 (p53BP2) is a protein that in humans is encoded by the TP53BP2 gene. Multiple transcript variants encoding different isoforms have been found for this gene The p53 tumor suppressor acts to integrate multiple stress signals into a series of diverse antiproliferative responses. One of the most important p53 functions is its ability to activate apoptosis, and disruption of this process can promote tumor progression and chemoresistance. p53 apparently promotes apoptosis through transcription-dependent and -independent mechanisms that act in concert.
p53's dual regulation of arrest versus apoptosis may underlie tumor-selective effects of anti-cancer therapy. p53's apoptotic effect has been suggested to involve both transcription-dependent and. P53 up-regulated modulator of apoptosis (PUMA), a pro-apoptotic BCL-2 homology 3 (BH3)-only member of the BCL-2 family, is a direct transcriptional target of P53 that elicits mitochondrial apoptosis under treatment with radiation and chemotherapy. It also induces excessive apoptosis in cardiovascular and/or neurodegenerative diseases. PUMA has been found to play a critical role in ovarian. p73 is a protein related to the p53 tumor protein. Because of its structural resemblance to p53, it has also been considered a tumor suppressor.It is involved in cell cycle regulation, and induction of apoptosis.Like p53, p73 is characterized by the presence of different isoforms of the protein p53 and DIRAS3 are tumor suppressors that are frequently silenced in tumors. In this study, we sought to determine whether the concurrent re-expression of p53 and DIRAS3 could effectively induce head and neck squamous cell carcinoma (HNSCC) cell death. CAL-27 and SCC-25 cells were treated with Ad-DIRAS3 and rAd-p53 to induce re-expression of DIRAS3 and p53 respectively p53 stands at the crossroads of cell death, growth, and differentiation and therefore sustains the homeostasis of individual cells, specific tissues, and entire organisms. p53 regulates apoptosis, proliferation, differentiation, angiogenesis, and cell-matrix interactions. 81,82 Each individual tissue and cell lineage incorporates a distinct balance among the various biologic processes mediated.
p53 mutants can form amyloid-like structures that accumulate in cells. p53 reactivation with induction of massive apoptosis-1 (PRIMA-1) and its primary active metabolite, 2-methylene-3-quinuclidinone (MQ), can restore unfolded p53 mutants to a native conformation that induces apoptosis and activates several p53 target genes. However, whether PRIMA-1 can clear p53 aggregates is unclear Sodium orthovanadate (vanadate) inhibits the DNA-binding activity of p53, but its precise effects on p53 function have not been examined. Here, we show that vanadate exerts a potent antiapoptotic activity through both transcription-dependent and transcription-independent mechanisms relative to other p53 inhibitors, including pifithrin (PFT) α However, overexpression of STING suppressed p53 Ser392 phosphorylation, p53 transcriptional activity, p53-target gene expression, and p53-dependent mitochondrial depolarization and apoptosis. In summary, our current study demonstrates that STING-mediated IFI16 degradation negatively regulates IFI16 mediated p53-dependent apoptosis in osteosarcoma and non-small cell lung cancer (NSCLC) cells. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (PubMed:12524540). However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (PubMed:12524540.
Viele übersetzte Beispielsätze mit p53-mediated apoptosis - Deutsch-Englisch Wörterbuch und Suchmaschine für Millionen von Deutsch-Übersetzungen Expression of genes in the NF-κ B/p53-apoptosis signaling pathway were analyzed after fibronectin siRNA transfection both in vitro and in vivo. Based on the results, high expression of fibronectin was observed both in the CRC tissues and CRC cell lines. The expression level was positively correlated with TNM stage (P=0.0025) and distant metastasis (P=0.0013). By Kaplan-Meier analysis, the. p53-like regulator of apoptosis and cell cycle Imported Gene names i: Name:p53 Imported. Synonyms: CG10873 Imported, CG31325 Imported, D-p53 Imported, Dm-P53 Imported, Dmel\CG33336 Imported, DMP53 Imported, DmP53 Imported, Dmp53 Imported, dmP53 Imported, dmp53 Imported, Dp53 Imported, dp53 Imported, P53 Imported, prac Imported. ORF Names: CG33336 Imported, Dmel_CG33336.
p53 Contributes to Quercetin-Induced Apoptosis in Human Rheumatoid Arthritis Fibroblast-like Synoviocytes | springermedizin.de Skip to main conten Therefore, the P53-mediated extrinsic Caspases apoptosis pathway and P53-mediated intrinsic Bax apoptosis pathway were both selected. The results showed that AE not only significantly up-regulated the mRNA expression of Caspase2 and Caspase3, but also significantly increased Bax and decreased Bcl-2 mRNA expression, which suggested that AE can cause apoptosis of zebrafish hepatocytes through. This study was performed to examine the correlation between mutations of the p53 tumor suppressor gene, the occurrence of apoptosis, and proliferation in cholangiocellular carcinoma of the liver. The results obtained were compared with p53 apoptosis effector related to PMP-22. Alternative name(s): Keratinocyte-associated protein 1. Short name: KCP-1. P53-induced protein PIGPC1. Transmembrane protein THW Gene names i: Name:PERP. Synonyms: KCP1, KRTCAP1, PIGPC1, THW. Organism i: Homo sapiens (Human) Taxonomic identifier i: 9606 : Taxonomic lineage i › Eukaryota › › Metazoa › › › › Chordata › Craniata. ID Gene Name Species CHROMOSOME CYTOBAND ENSEMBL_GENE_ID GENERIF_SUMMARY OFFICIAL_GENE_SYMBOL OMIM_DISEASE SP_COMMENT RELA proto-oncogene, NF-kB subunit(RELA) RELA.
p53 is a tumor suppressor protein important in the regulation of apoptosis. Because p53 functions as a transcription factor, cellular responses depend upon activity of p53 localized in the nucleus. Cytoplasmic sequestration of p53 has been proposed as a mechanism by which the function of this protein can be suppressed, particularly in tumor types such as neuroblastoma in which the frequency of. Publisher Summary Recent research in apoptosis has crossed the boundaries into the fields of tumorigenesis and antineoplastic therapy. It is becoming overwhelmingly apparent that the same defects in tumor cells that promote their inappropriate growth and survival can contribute to their resistance to therapy. The p53 protein was first identified as a cellular phosphoprotein that. Aim: To investigate whether p53 expression and apoptosis play a role in the pathogenesis of discoid lupus erythematosus (DLE) and whether they are associated with a hyperproliferative state in the epidermis of DLE lesions and epidermal atrophy. Methods: A total of 70 skin biopsy specimens, 35 DLE and 35 normal, were used. Expression of protein p53 and Ki-67 was examined immunohistochemically Goji berry (Lycium spp.) extracts exhibit antiproliferative activity via modulating cell cycle arrest, cell apoptosis, and the p53 signaling pathway † Lei Xiong, a Na Deng, * a Bisheng Zheng, ab Tong Li c and Rui Hai Liu* c Author affiliations * Corresponding authors a Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health (111 Center), School of.
smoke; p53; apoptosis; oxidative stress Introduction Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease with a high morbidity and mortality, which places a serious burden on society and has become an important public health problem (World Health Organization 2014). Emphysema is the main pathological feature of COPD. Smoking is a major and most important risk. View P53 Apoptosis PPTs online, safely and virus-free! Many are downloadable. Learn new and interesting things. Get ideas for your own presentations. Share yours for free P53, as a regulating apoptotic protein, its major function has always been changed since 1979 when this protein was first reported. p53 could mediate cell cycle arrest and DNA damage, which is an important factor for apoptosis . p53 could play an important regulator in cell apoptosis and tumorigenesis Although the p53-independent mechanism activated by GALR2 has not yet been clearly defined, it is known that some kinds of receptors and signaling proteins, such as adenovirus E1A, E2F1, and p73, induce apoptosis independent of p53 (34-37). Conflicting results have been reported regarding GPCR-induced apoptosis and p53 status
PUMA (p53 upregulated modulator of apoptosis), a BH3-only Bcl-2 family protein, was recently identified as a transcriptional target of p53 and a potent apoptosis inducer in various cancer cells. In this study, we showed that the induction of PUMA by cisplatin was abolished in p53-deficient SKOV3 cells. Elevated expression of PUMA-induced apoptosis and sensitized A2780s and SKOV3 ovarian cancer. Through direct cloning of p53 ()-binding sequences from genomic DNA using a yeast enhancer trap system, Oda et al. (2000) isolated a gene, which they called p53AIP1 (p53-regulated apoptosis-inducing protein-1), whose expression was inducible by wildtype p53.The p53AIP1 gene has 3 major transcripts, designated alpha, beta, and gamma, which encode proteins of 124, 86, and 108 amino acids.
Accordingly, p53-dependent induction of PUMA, a critical mediator of p53-dependent neuronal apoptosis (Uo et al., 2007), was identified as a target of HDACI action upstream of Bax activation. The expression of PUMA was almost completely dependent on both p53 and HDAC activity, and PUMA mRNA induction subsequent to HDACI removal in CPT-treated neurons did not require new protein synthesis p53 is the most important tumor-suppressor gene, and is implicated in regulation of apoptosis; its protein is activation is controlled by post-translational modifications, such as phosphorylation, acetylation, and interactions with other proteins. p53 phosphorylation not only stabilizes and enhances the transcription activity of p53, but also regulates its subcellular localization. p53 serine. At the cellular level, the combination of metformin and 2DG induced p53-dependent apoptosis via the energy sensor pathway AMP kinase, and the reexpression of a functional p53 in p53-deficient prostate cancer cells restored caspase-3 activity. In addition to apoptosis, the combination of metformin and 2DG arrested prostate cancer cells in G2-M. This G2-M arrest was independent of p53 and.
