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"Since most cervical tumors are infected with HPV, and the tumors originate through p53 gene mutation caused by the said interaction, which leads subsequently to the overexpression of p53 oncoprotein, lack of the latter in the remaining 11 cervical tumors may either be the result of technical shortcomings, or the tumor may arise in such circumstances through a p53 independent pathway."
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"Further, all cells transduced with ncmDeltaNGFR-huARF were positive for p53 driven beta-gal activity (XREF_FIG) and expression of p53 activating molecules resulted in a lower overall proportion of transduced cells at 68h after transduction (XREF_FIG), indicating that the growth rate of cells transduced with p53 activating molecules was slowed."
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"Furthermore, efficient stable knockdown of p53 in TPC-1 (TPC-1 sh-p53) cells effectively abrogated expression of p53, p21, MDM2, and PUMA in response to APG115 treatment, whereas stably transfected negative control shRNAi TPC-1 (TPC-1 sh-NC) cells did not cause concentration dependent upregulation of those proteins."
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"While our previous work has demonstrated that p68 stimulates expression of p53 target genes that are normally induced by activated p53, we reasoned that, in a different transcriptional context (i.e. the p53 intron 4 promoter), p68 might act to repress p53 transcriptional activity, having previously shown that p68 can, in some contexts, repress transcription."
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"In addition, using DNAJA1-knockdown HN31 cells by a DNAJA1-shRNA and DNAJA1-knockout HN31 cells, generated by another CRISPR-Cas9 system used in Supplementary Fig. S2B, C, we confirmed that overexpression of DNAJA1 or mutp53 rescued mutp53 levels and migratory potential of DNAJA1-depleted HN31 cells (Supplementary Fig. S3A, B)."
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"We conclude that (i) miR-125b and miR-150 target p53, which in turn regulates RelA and NFkB and miR-146a expressions; (ii) reduced miR-125b and miR-150 expressions, increased p53 level and decreased RelA and NFkB and miR-146a expressions originate from mutant HTT (iii) p53 directly or indirectly regulates the expression of miR-146a."
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"By direct binding, JNK also targets p53 for ubiquitin mediated degradation involving Mdm2-p53 degradation pathway Therefore, inactivation of JNK by anti-sense JNK1 or SP600125 would decrease the amount of JNK-p53 and/or Mdm2 and p53 complex to increase the steady state level of p53 by preventing p53 degradation in non stressed cells."
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"These results demonstrate that the p53 mRNA NPs effectively restored p53 expression in vivo and significantly enhanced the anti-tumor effects of aPD1 therapy in HCC growing outside the liver.Using the same model, we also harvested tumors and lymph nodes to examine the number and phenotype of immune cells and the changes in secreted cytokines after four cycles of treatment."
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"Remarkably, treatments with UV radiation, CDK inhibiting (flavopiridol, DRB, roscovitine), transcription inhibiting (actinomycin D), and p53 inducing compounds (doxorubicin, etoposide, nutlin-3) not only increase p53 levels [XREF_BIBR, XREF_BIBR, XREF_BIBR], but also enhance the protein protein interactions between HEXIM1 and p53 (XREF_FIG) [XREF_BIBR]."
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"To further investigate the role of RNF20 and RNF40 in p53 stabilization and transcription of p53 target genes, p53 protein expression levels were analyzed using western blot analysis, and the relative mRNA expression levels of p53, p21, PUMA, mash1 and Oct4 genes were determined using RT-qPCR in RNF20- or RNF40-knockout cells."
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"This suggestion is supported by our finding that treatment of mice with the USP7 inhibitor P5091 effectively eliminated SnCs and reduced the expression of SASP factors caused by DOX.In conclusion, we reveal that USP7 is a novel senolytic target, and USP7 inhibition can selectively kill some SnCs with p53 downregulation in vitro and clear SnCs induced by chemotherapy in mice in part by destabilizing MDM2 to increase p53 expression."
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"This data shows that transfection of an siRNA targeting p53 reduces p53 levels in DLD-1 cells prior to adriamycin treatment, as well as limiting the ability of these cells to fully recover p53 levels as a function of increasing adriamycin concentrations, despite the fact that the increase in p53 levels following DNA damage occurs through post-translational stabilization of p53 protein."
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"Geminin depletion induces DNA re-replication in cancer cells, regardless of the presence or absence of the tumor suppressor protein p53, but p53 +/+ cancer cells induce expression and phosphorylation of p53, as well as expression of the CDK specific inhibitor p21 whose transcription is p53 dependent [; XREF_FIG]."
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"Given the opposing responses of MDM2 and p53 elicited by HB-EGF (Fig. 3A), the enhanced association of p53 and MDM2 by HB-EGF stimulation (Fig. 3B) supported the hypothesis that MDM2 may negatively regulate p53 expression, possibly by stimulating direct binding of MDM2 to p53 following HB-EGF treatment [33]–[35]."
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"Taken together, the evidence suggests that CTCE-targeted NPs demonstrated significantly enhanced cellular uptake, mRNA transfection efficiency, and intratumoral accumulation compared to non-targeted NPs irrespective of tumor site/stroma, supporting the use of CTCE peptide ligands for selective HCC cell targeting.To determine whether the targeted p53-mRNA NPs could induce the expression of therapeutic p53 in p53-null RIL-175 cells, we first checked p53 protein expression after treatment with CTCE-p53 NPs versus SCP-p53 NPs."
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"Although there was no significant difference in expression of CDKN1A, VDR, and TP53INP1 between CD24 + PC3 cells and CD24 - PC3 cells, the transfections of WT TP53, mutants TP53 R273H, TP53 V143A, and TP53 R280T, but not mutant TP53 R175H, induced the expression of these p53 target genes in CD24 - PC3 cells but not in CD24 + PC3 cells (XREF_FIG)."
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"Mutations in ihc p53 gene increases tlte level of p53 expression in ihe cell and create new MHC I restricied epitopes for T cell recogniUoa Furtliemiore, ihc upregulation of wild type p53 epitopes might exceed the level of expression required for activation of autoreactive tumor specific T cells.We selected peptides derived from the p53 sequence and tested ihclr binding to HLA-A2.1 molecules, using a biodiemical assay."
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"Since the p53 related transcription factors p63 and p73 can modulate p53 functions and activate the transcription of some p53 target genes XREF_BIBR, XREF_BIBR, we examined the impact at the FLT1 promoter alleles using gene reporter assays and ectopic expression of p53 or of selected p63 and p73 isoforms."
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"PPMD1, a member of the PP2C family of Ser/Thr protein phosphatases that is induced in a p53 dependent manner in response to various environmental stresses, reduces the phosphorylation of p53 through negative regulation of p38 MAP kinase, and in turn suppresses p53 mediated transcription and apoptosis."
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"P53 translation negative regulators including miR-125b, miR-25 and nucleolin inhibit p53 expression and positive regulators including HuR and heterogeneous nuclear ribonucleoprotein (hnRNP) Q enhance p53 expression and p53 mediated apoptosis and cell cycle arrest [XREF_BIBR, XREF_BIBR - XREF_BIBR]."
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"In contrast, p53 25,26,53,54 combined with wild-type p53 drove elevated expression of select p53 target genes, including Noxa and Pidd, but not p21 and Mdm2, relative to levels in p53 +/- and p53 +/+ MEFs, suggesting that p53 25,26,53,54 activates wild-type p53 to induce expression of specific p53 target genes (XREF_FIG, XREF_FIG)."
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"Our results suggest that p53 may block oncogenic transformation by decreasing BCL6 stability via caspase-1 up-regulation, whereas aberrant BCL6 expression inactivates transactivation of p53 target genes, either by inhibiting p53 acetylation by p300 or repressing TP53 gene transcription."
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"The results indicated that, although cells overexpressing p53β significantly enhanced the luciferase activity for all three promoters, those that overexpressed p53γ showed only a modest increase for p21 and GADD45A promoters (Fig. S7), suggesting that, in the absence of p53α, overexpression of p53γ alone is not sufficient to increase the expression of these p53 transcriptional targets."
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"Background:.
A transversion missense polymorphism of the TP53 tumor suppressor gene at the codon 72 codes proline instead of arginine causes an altered p53 protein expression and has been found to be associated with an elevated risk of various cancer; especially breast and lung cancer."
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"With the exciting findings of the reciprocal regulation of p53 by RBPs, such as the RBM38/HuR/MDM2/p53 regulatory loop, our knowledge of the complex regulation of p53 and the p53 network allows for the potential intervention with therapeutic approaches to upregulate the expression of p53, or p53 targets like p21."
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"The results showed that overexpression of p53 significantly elevated the protein level of p53 in A549 and PC-9 cells (Figure 4A) and led to the growth of A549, and PC-9 cells were inhibited (Figure 4B), but after interfering with siRNA of p53, the protein level of p53 was dramatically decreased (Figure 4A), and accordingly, the proliferation of A549 and PC-9 cells was promoted instead (Figure 4B)."
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"Hence, these results demonstrate that infection of RGNNV induces p53-dependent G1 delay.To determine whether RGNNV infection induced p53-dependent G1 arrest by mediating p53 level and activity, we analyzed p53 levels after RGNNV infection in GS cells by immunofluorescence staining and Western blot analysis."
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"Moreover, by using western blot analysis, we determined that EA increased the protein expression of the p53 target proteins p21, p53 upregulated modulator of apoptosis (PUMA) [also known as Bcl-2-binding component3 (BBC3)] and Phorbol-12-myristate-13-acetate-induced protein 1 (NOXA)."
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"At the same time, the expression of p53 which is known as a tumor suppressor and p21 which prevents cell proliferation were increased by 2.5- (p53) (P < 0.01) and 2-fold (p21) (P < 0.01) at 0.1 mug/mL of BA-TPQ-hydrogel treatment, and by 3.9- (p53) (P < 0.01) and 3.2-fold (p21) (P < 0.01) at 0.5 mug/mL of BA-TPQ-hydrogel treatment (XREF_FIG), respectively."
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"Akt inactivation reduces the degradation of p53, which ultimately leads to the increased expression of p21 and p53, and inhibition of tumor progression, indicating that tanshinone induces apoptosis through the mitochondrial apoptosis pathway and inhibition of the PTEN mediated PI3K and Akt pathway for effectively inhibiting tumor growth."
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"In HUVEC, we previously demonstrated that P4 binds to PR, subsequently activating the cSrc/Kras/Raf-1/ERK2 signaling cascade to increase NFkappaB nucleus translocation and binding onto the p53 promoter, which in turn up-regulates the expression of p53, eventually resulting in the inhibition of endothelial cell proliferation."
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"Objective: The present study aimed to explore the expressions of long noncoding RNA (lncRNA) p53 upregulated regulator of p53 levels (PURPL) in different ovarian tissues, and to evaluate the significance of disregulations of PURPL and microRNA-338-3p (miR-338-3p) in epithelial ovarian cancer (EOC)."
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"Consequently, when we blocked the expression of miR-1228, p53 was released and enforced the inhibition of miR-1228, thereby promoting the accumulation of p53; however, miR-1228 is upregulated in HCC tissue in which p53 is downregulated, repressing p53 expression to relieve its inhibition on miR-1228 expression in turn, which creates a feedback regulation to ensure persistent low protein levels of p53 to control the malignant phenotype."
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"In a feedback fashion, they work together to directly inhibit the transcriptional activity of p53 and mediate p53 degradation via ubiquitin dependent proteolysis, as MDM2 possesses an E3 ubiquitin ligase activity and its mRNA expression is stimulated by p53, thus, keeping p53 level and activity marginally detectable in most of normal mammalian cells or tissues."
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"However, p53 re-expression almost completely suppressed expression of Cyclin B1 and inhibited BKM120 mediated activation of MEK1/2, indicating that besides upregulation of p21, reduced MEK1/2 activation and suppression of Cyclin B1 contribute to the inhibition of BKM induced polyploidy by p53."
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"The conditional activation of p53 in VE-cadherin + vascular niche cells by deleting Mdm2 induced the expression of p53 target genes specifically in vascular endothelial cells, resulting in the dilation and collapse of vascular endothelial cells and reductions in perivascular mesenchymal stromal cell numbers."
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"Our findings unravel distinct patterns of K63 linked ubiquitination of p53 in various cellular compartments, which serves as an important molecular switch that enables p53 transcriptional activation in the nucleus and p53 transcription independent function in the mitochondrial for apoptosis under stress conditions."
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"In this study, the presence of Dox in INO80 silencing p53 +/+ HCT 116 cells also increased the protein level of p53 including p53-S15p and p21 (XREF_FIG), suggesting the up-regulation of p21 by INO80 chromatin remodeling complex might be associated with cell cycle phase G2/M checkpoint and abnormal chromosome stability."
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"Interestingly, we did not recognize an increase of p53 mRNA levels (data not shown), which suggests that the potential p21 mediated effect on the cell cycle may be independent of p53 or that the effect is executed by p21 rather than p53 as already shown in another study [XREF_BIBR]."
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"Functionally, p73, a family member of p53, activates transcription of p21- and p53 responsive genes, which participate in cell cycle control, DNA repair, and apoptosis and inhibits cell growth in a p53 like manner by inducing apoptosis or G1 cell cycle arrest XREF_BIBR, XREF_BIBR."
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"In response to cellular stresses such as DNA double-strand breaks, hypoxia, and inappropriate oncogene activation, the p53 transcription factor is stabilized within the cell and induces the expression of various p53 target genes involved in cell cycle arrest, apoptosis, and senescence."
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"Focusing our attention on P53, a critical modulator of Bcl2 family members , we have found that: (i) TP53 mRNA overexpression in HTLA-ER cells is not accompanied by an increase in the protein level (Figs 2 and 3 supplementary); (ii) the amount of P53 protein is high and not inducible in either cell line (Fig. 2); and (iii) MDM2, the primary negative regulator of P53 (Fig. 4 supplementary) , is not amplified in either cell population."
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"27 Even in the absence of keratinocytes, there is a strong melanogenic response to UVR mediated by p53 in human melanocytes and melanoma cells in vitro, which can be explained by the fact that p53 regulates the transcription of the hepatocyte nuclear factor 1alpha (HNF1 alpha), a tyrosinase transcription factor, in melanocytes."
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"Although it was not possible to sequence the TP53 gene in all 253 patient samples, IHC for p53 is a proxy for its mutational status, as most deleterious mutations in TP53 typically cause complete loss or destabilization of p53 protein expression, leading to an " all or nothing " IHC staining pattern."
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"We found that the protein expression of PI3K, p-AKT1 (S473), AKT1, and p53 in nuclei and cytoplasm showed that H O increased nuclear p53 protein level but decreased the protein levels of PI3K, p-AKT1 (S473), and AKT1; in contrast, this effect was rescued by overexpression of IGF-1 with adenovirus vector via activating the PI3K/AKT1 pathway in cytoplasm (Fig. 6a)."
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"These results may be due, in part, to the presence of immune cells, such as activated lymphocytes expressing WT p53 at levels comparable to some tumor cells, wherein further increase of p53 expression by p53 SMWC may alter survival of these immune cells and negatively impact an effective immune response."
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"Methylation, mutations, and CNAs have complicated effects on downstream gene expression: for instance, inactivating mutations in TP53 can increase TP53 levels through a feedforward mechanism (Marks et al., 1991; Rodrigues et al., 1990), while certain chromosomal amplifications can fail to increase protein expression due to dosage compensation (McShane et al., 2016; Schukken and Sheltzer, 2021)."