"The cytosolic quinone oxidoreductases [NRH:quinone oxidoreductase 2 (NQO2) and NAD(P)H:quinone oxidoreductase 1 (NQO1)] interacted with p53 and protected p53 against 20S proteasomal degradation."
"Western blot analysis revealed that the endogenous p53 expression was markedly reduced by infection of p53 siRNA (p53-siRNA) but not scrambled siRNA (Scr-siRNA) (XREF_FIG, left)."
"The tumor-suppressive role of miR-34a was confirmed by Luan et al. who also found that miR-34a levels reflect the status of tumor suppressor p53, and that miR-34a could activate the p53 signaling cascade of p53 expression independently, possibly through targeting of SIRT1 [XREF_BIBR]."
"Thus, overexpression of these kinases in tumors prevents the degradation of both p53 and Mdm2, ultimately increasing p53 expression."
"The results showed that p53 siRNA markedly reduced the protein expression of p53 in A549 cells (XREF_FIG)."
"Expression of tumor suppressor p53 and the cell cycle regulatory protein p21 was stimulated within 5 to 10 min by cisplatin in p53 positive LX-1 small cell lung carcinoma cells, and this effect was blocked by NAC."
"PCNA and DDB1/CUL4A complexes were found to physically interact with p53 tumor suppressor and its regulator MDM2/HDM2. The isolated CUL4A complexes display potent and robust polyubiquitination activity towards p53 and this activity is dependent on L2DTL, PCNA, DDB1, ROC1 and MDM2/HDM2."
"To investigate possible pathways linking Gas2 to p53, a yeast two-hybrid screen swas performed, indicating m-calpain as a strong Gas2- interacting protein. Moreover, we demonstrate that Gas2 physically interacts with m-calpain in vivo and that recombinant Gas2 inhibits calpain-dependent processing of p53."
"In fact, even though it has been reported that IL-6 activates STAT3 18 and that activated STAT3 binds to the TP53 gene promoter repressing the transcription of TP53 mRNA, 19 we found that no significant change occurred in the transcription level of TP53 mRNA in the NCM460, HepG2, SW1990 and LS174T cell lines (XREF_FIG)."
"Compared to the nontargeting control, silencing candidate inhibitors of p53 activity increased p53 protein levels in A549 cells, except for HNRNPL and SOS1."
"ultimate carcinogen benzo[a]pyrene diol epoxide (BPDE) Analyses of proteins in treated cells indicated that p53 was phosphorylated at Ser15 but not at Ser20 within 30 min of treatment, and this correlated with an increase in the total amount of p53 protein."
"Although p53 siRNA alone reduced the expression of p53 mRNA (XREF_FIG), there was no reduction of p53 expression at the protein level (XREF_FIG)."
"As shown in XREF_FIG, the p53 shRNA construct significantly down-regulated p53 protein expression in the Tu138 cells as compared to vector control cells."
"Here we show that the wild-type p53 induced phosphatase 1 (Wip1), or PPM1D, downregulates p53 protein levels by stabilizing Mdm2 and facilitating its access to p53."
"In vitro, nuclear p14arf stabilizes nuclear p53 nuclear p14arf binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53"
"There was a significant reduction (ranging from 22% -30%) in endogenous levels of the cleaved caspase-3 protein when either the MEK and ERK pathway or the mitochondrial arm of the p53 pathway was suppressed, indicating that while the p53 protein likely influences apoptosis, as induced by B. burgdorferi in mature MO3.13 human oligodendrocytes, the MEK and ERK pathway affects inflammation, p53 levels, and apoptosis."
"However, p53 mediated transactivation of WAF1 and p21 was impaired in the wild-type p53 expressing tumours that expressed elevated levels of MDM2."
"Mdm2 has long been considered a major p53 regulator that inhibits p53 mainly through ubiquitination followed by proteasomal degradation ( 1"
"When p53 expression was inhibited by p53 siRNA or PFT, the decreases of G1 phase in response to B (a) P treatment still existed, and over expression of p21 induced by B (a) P was attenuated, especially in nuclear, but E2F-1 over expression was not changed significantly."
"Both VRK2 isoforms have an identical catalytic N-terminal domain and phosphorylate p53 in vitro uniquely in Thr18. Phosphorylation of the p53 protein in response to cellular stresses results in its stabilization by modulating its binding to other proteins."
"Microarray analysis identified upregulation of several microRNAs (miR-1249-5p, miR-6737-5p, and miR-6819-5p) in TP53 deficient CDEs, which were functionally proven to suppress TP53 expression in fibroblasts."
"Moreover, TP53 was significantly down-regulated in radioresistant NPC samples and decreased TP53 expression reportedly enhanced the radioresistance of some solid tumours 39, 40."
"Our results propose that a balanced ratio of MDM-2 and p53 will allow cells to tolerate a limited expression of wt p53."
"The induction of p53 strand breaks by folate depletion does not impair p53 expression or action within all human cell lines."
"Substitution of Thr-55 with an alanine residue (T55A) stabilizes p53 and impairs the ability of TAF1 to induce G1 progression."
"p16(INK4a) is a critical component in retinoblastoma protein (Rb)-mediated growth regulatory pathway, p14(ARF) plays a pivotal role in the activation of p53 upon oncogenic stress signals."
"As a potent inhibitor of glycolysis, wild-type p53 downregulates glucose uptake and promotes expression of the tumor suppressor TP53 inducible glycolysis and apoptosis regulator (TIGAR)."
"Knockdown of p53, as expected, decreased the expression of p53 regulated genes, miR-34c and miR-200a (P < 0.01, n = 3)."
"As shown in XREF_FIG, the p53 siRNA almost completely depleted p53 protein expression and eradicated p21 WAF1 induction upon FOXF1 knockdown, consistent with the data from the HCT116-p53-/- cell line (XREF_FIG)."
"Three novel single nucleotide variants were shown to disrupt miR-125b binding to their TP53 target causing upregulation of p53 expression and an increase in apoptosis, while in contrast the rs78378222 CC SNP located in the polyadenylation signal (PAS) and not a putative miRNA binding site, was shown to reduce p53 expression and subsequently reduced apoptosis."
"Our data indicate that wt p53 at basal levels does not bind its target sites and that the presence of a mt p53 can block elevated levels of wt p53 from binding target promoters."
"In concert with these results, Lyn reverses Mdm2-mediated degradation of p53 and increases p53-dependent apoptosis. Our findings support a previously undefined role for nuclear Lyn in both activation and Mdm2-mediated regulation of p53."
"We found that 14-3-3 sigma interacted with p53 in response to the DNA-damaging agent adriamycin. Importantly, 14-3-3 sigma expression led to stabilized expression of p53."
"The si-p53 transfection reduced the level of p-p53 increased by Cr (VI) to the basal level (XREF_FIG)."
"Inactivation of endogenous YY1 enhances the accumulation of p53"
"Stable p53 knockdown cells were also generated in MOLM-13 and MV4-11 cells, and p53 specific short hairpin RNA reduced p53 levels by 69% and 90%, respectively."
"the central module is the interplay between p53 and the Mdm2 protein, which inactivates p53 and targets it for rapid proteolysis."
"p53 shRNA was used to stably reduce p53 levels in MCF-7 cells, in order to examine the re-expression of either p53 or a p53 mutant that evades defective DACH1 binding."
"The loss of p53 and the acquisition of the immortal phenotype can be accelerated by the treatment of p53 +/- LFS fibroblasts with the chemical carcinogen aflatoxin B1."
"p53 siRNA was used to abolish p53 expression in RNC cells and further these cells were used to generate RNC p53-Lys 118 (Mut) cells upon stable transfection with p53 cDNA carrying Lys 118 -Ala 118 point mutation."
"we find that expression of Akt reduces the protein levels of p53, at least in part by enhancing the degradation of p53."
"The turnover rate of p53 is normally high in HeLa cells, but in the presence of miR-29 miRNAs (MIR29A, MIR29B1, MIR29C) p53 became more stable."
"In either case, alterations in p53 function, diminished p53 protein levels, and abnormal karyotypes were evident, irrespective of time or tumor model."
"As shown in XREF_FIG, the p53 shRNA effectively reduced endogenous p53 expression in both A549 and H1666 cells."
"Wild-type p53 induced phosphatase 1 (WIP1) downregulates p53 expression and has been shown to be overexpressed in MBs."
"While 13% of MM patients carry TP53 coding mutations or 17q13.1 deletion causing allelic loss of TP53, 24% of plasma cell leukemia (PCL) patients have TP53 coding mutations and 50% of primary PCL patients or 75% of secondary PCL patients have 17q13.1 deletion."
"Our finding of p53 's being one of the most downregulated proteins in DDW treatment is consistent with the previous reports of DDW suppressing the p53 expression in different organs of animals, including the lungs."
"In vitro phosphorylation of p53 by JNK abolished Mdm2 binding and targeting of p53 ubiquitination"
"It is evidenced that p53 depletion via siRNA transfection can effectively reduce the expression level of p53 and its downstream molecular, including p21, cdc2, and cyclin B1 (XREF_FIG)."
"Inhibition of E6 should block its ability to promote the degradation of p53 thereby increasing the levels of p53."
"The tp53 knockdowns restored normal p21 and tp53 expression in flo larvae."
"p53 kbhb attenuates p53 acetylation levels, as well as the transcriptional activity of p53 at canonical p53 target genes, including p21 and PUMA, thereby reducing the effects of p53 on cell apoptosis and cell growth."
"Although this has not been reported earlier, this could be explained by common mutations in p53 in these subtypes of breast cancer, perhaps preventing p53 mediated transcription of mir-34."
"p14ARF tumour suppressor stabilises and activates p53 by directly interacting with (H)Mdm2 [(human) murine double minute 2 homologue] and inhibiting its E3 ubiquitin ligase activity. Expression of p14ARF protects p53 from (H)Mdm2-mediated ubiquitylation but has no effect on the auto-ubiquitylation activity of (H)Mdm2 ."
"Moreover, inhibition of p53 either by adenovirus mediated overexpression of DN-p53 or treatment with the p53 inhibitor pifithrin-alpha (PFTalpha) reversed defective GSIS in MDM2 deficient islets (XREF_FIG)."
"Co-incubation with pifithrin-alpha (PFT-alpha), a specific inhibitor of p53, restored Bcl-2, p53 and p21WAF1 levels to the untreated control and suppressed TQ induced cell cycle arrest and apoptosis."
"The transfection of p53 siRNA efficiently abrogated both p53 expression and p53 induction upon treatment with arenobufagin."
"These results suggest that a ' slipped mispairing ' mechanism occurring during DNA replication may generate p53 intragenic deletion in human esophageal cancer, leading to abolished p53 mRNA expression."
"Importantly, as with the K-ras LSL-G12D allele, the LSL cassette in p53 LSL-mt alleles blocks p53 expression in the absence of Cre, effectively creating a p53 null allele."
"Inhibition of P53 in melanocytes induced changes in P53 target gene expression that were characteristic of melanoma cells and resulted in increased proliferation."
"As shown in Fig XREF_FIG E, p53 reduction by NAT10 knockdown was rescued by addition of MG132, revealing that NAT10 regulates p53 levels through proteasome dependent pathway."
"Furthermore, hEcd interacts with murine double minute-2 and stabilizes p53 by inhibiting murine double minute-2-mediated degradation of p53"
"MDM2 functions as an E3 ubiquitin ligase to degrade p53"
"This indicates that TP53 truncating mutations reduce TP53 expression but some non truncating mutations are capable of increasing it."
"The depletion of p53 decreased the amount of p53 and also the induction of p21 by doxorubicin (XREF_FIG, lanes 3-4)."
"We reasoned that specific inhibition of Mdm2 mediated proteasomal degradation of p53 might further enhance p53 levels."
"Interaction of Jab1 with the tumor suppressor p53 induces CSN-mediated phosphorylation and subsequent degradation of p53 (Bech Otschir et al., 2001)."
"Furthermore, we found that FIP200 could interact with exogenous and endogenous p53 protein and significantly increase its half-life compared with the control cells ... from full text, U2OS cells"
"In contrast, as expected, silencing TP53 reduced p53 and CDKN1A protein levels."
"The Mdm2 Tg mice carrying an integrated Mdm2 cosmid, expressing an average 4-fold of Mdm2 compared to that of wild-type mice, are tumor prone, while the p53 Neo and Neo mice inheriting a hypomorphic p53 allele have decreased expression of wild-type p53 and are also tumor prone."
"Finally, the p53 antisense oligodeoxynucleotide, which inhibits the expression of wild-type p53, also induces a decrease of the MDM2 level in cells, whether or not they overexpress this protein, and causes apoptosis of these cells."
"despite being expressed at comparable levels (see Fig. 6A), S395D was far less capable of promoting p53 degradation"
"Immunoblot analysis indicated that transfection of p53 specific siRNA depleted the p53 level by 80% and did not affect the p65 level (XREF_FIG)."
"YY1 overexpression stimulates p53 ubiquitination and degradation."
"p53 specific shRNA reduced p53 levels by> 85%."
"We demonstrated that inactivation of p53 by p53 specific siRNA significantly inhibits the expression of p53 targeted genes (i.e. p21 and Bax) and alleviated alcohol induced cell cycle arrest (XREF_FIG)."
"Here, we report that Synoviolin targets tumor suppressor gene p53 for ubiquitination. Synoviolin sequestrated and metabolized p53 in the cytoplasm and negatively regulated its cellular level and biological functions, including transcription, cell cycle regulation and apoptosis."
"Transinfection of p53 serine could inhibit the expression of p53 in uveal melanoma and the invasion ability of the cells."
"Hr expression lowered levels of p53, p53 mediated reporter gene activity, and lower levels of the pro apoptotic Bcl2 family member Bax in COS cells."
"Furthermore, blocking expression of wtp53 in OCI-AML3 cells by treating them with a small interference RNA against p53 (sip53), which effectively decreased p53 expression (XREF_SUPPLEMENTARY), prevented DCA induced decreased daunorubicin clearing, whereas a control siRNA did not show any effect (data not shown)."
"p53 siRNA abrogated the SBHA induced apoptosis and the expressions of p53, p21, Bax, and PUMA."
"Lentivirus-siRNA P53 was then used to reduce endogenous p53 levels in HepG2 cells and found that HepG2-p53 RNAi cells treated with rAdV-TK and GCV alone exhibited more viability than HepG2-p53 RNAi cells treated with rAdV-p53 and rAdV-TK and GCV (XREF_SUPPLEMENTARY)."
"The investigators hypothesize that, by inhibiting MDM2 expression, the MDM2 oncoprotein level will be reduced and the MDM2 negative feedback inhibition of p53 will be diminished, resulting in a significant increase of functional p53 levels that will modulate p53 mediated therapeutic effects."
"Finally, instead of down-regulation of FOXM1 expression as observed in Detroit 562 and Ca9-22 cells (XREF_FIG), decreasing the p53 level by p53 shRNA in STAR cells, which contain endogenous wild-type p53, increased the levels of FOXM1 (XREF_FIG), suggesting that wild-type p53 inhibits FOXM1 expression."
"We investigated the role of the ubiquitin-conjugating enzyme UBCH7 in nuclear receptor transactivation. Using transient transfection assays, we demonstrated that UBCH7 modulates the transcriptional activity of progesterone receptor (PR) and glucocorticoid, androgen, and retinoic acid receptors in a hormone-dependent manner and that the ubiquitin conjugation activity of UBCH7 is required for its ability to potentiate transactivation by steroid hormone receptors (SHR). However, UBCH7 showed no significant effect on the transactivation functions of p53 and VP-16 activation domain. Depletion of endogenous UBCH7 protein by small interfering RNAs suggests that UBCH7 is required for the proper function of SHR. Furthermore, a chromatin immunoprecipitation assay demonstrated the hormone-dependent recruitment of UBCH7 onto estrogen receptor- and PR-responsive promoters. Additionally, we show that UBCH7 and E6-associated protein (E6-AP) synergistically enhance PR transactivation. We also demonstrate that UBCH7 interacts with steroid receptor coactivator 1 (SRC-1) and that UBCH7 coactivation function is dependent on SRC-1. Taken together, our results reveal the possible role of UBCH7 in steroid receptor transactivation and provide insights into the mechanism of action of UBCH7 in receptor function."
"Abrogation of p53 expression by p53 small interfering RNA significantly attenuated 6-DG-induced DR5 expression, thus rendering these cells resistant to TRAIL induced apoptosis."
"together to form a ternary complex. We show that, when overexpressed, L23 inhibits HDM2-induced p53 polyubiquitination and degradation and causes a p53-dependent cell cycle arrest."
"We exploited the conditional nature of the XTR system to determine if somatic recombination of p53 XTR and XTR to p53 TR/TR would inactivate p53 expression and lead to rapid onset of lymphoma in Emu-Myc transgenic mice."
"Western blotting confirmed that p53 levels were reduced specifically by the p53 shRNA, and that this remained the case following ARF induction with IPTG (XREF_FIG A)."
"BCL6 and p53 function in a negative-feedback loop whereby p53 promotes BCL6 expression, which in turn suppresses the expression of TP53."
"HER-2/neu-mediated resistance to DNA-damaging agents requires the activation of Akt, which enhances MDM2-mediated ubiquitination and degradation of p53."
"Upon DNA damage, the amino terminus of p53 is phosphorylated at a number of serine residues including S20, a site that is particularly important in regulating stability and function of the protein."
" p53 is rapidly degraded by the process of ubiquitiation and proteasome. mdm2 stimulates p53 degradation"
"We used p53 siRNA to inhibit p53 expression and observed that p53 knockdown failed to downregulate CHOP expression in Hep1-6 (XREF_FIG) and HepG2 cells (XREF_SUPPLEMENTARY)."
"auroraA is known to phosphorylate p53, which leads to its ubiquitylation by MDM2 and subsequent proteolysis"
"Two stable clones of a HT1080 fibrosarcoma cell line, differing only in p53 status due to RNAi mediated knockdown of p53 expression, were incubated for 1 h with [(1) (1) (1) In]-oxinate (0-10 MBq/ml)."
"Western blots revealed that p53 was stabilized in HCT116 PTEN(-/-) cells via an Akt1-dependent and p14(ARF)-independent mechanism"
"In addition, downregulation of p53 protein expression by transfection of p53 specific siRNA markedly restored SIRT1 expression to normal control levels via decrease in miR-34a in the cisplatin treated HEI-OC1 cells."
"TP53 specific shRNA reduced p53 levels by approximately 90% (XREF_SUPPLEMENTARY)."
"HIF-1alpha induction was observed in cells expressing WT p53, where LPA decreased p53 expression."
"Thus, knockout of p53 in murine astrocytes strongly reduced the expression of MGMT, and, paradoxically, enforced expression of wild-type p53 in human tumour cells also reduced the transcription of the MGMT gene."
"Furthermore, downregulation of p53 expression by p53 siRNA significantly reduced Brefeldin A induced apoptosis in MCF-7 cells."
"In conclusion, the present study showed that Ad-p53 directly arrests the proliferation of HSCs by modulating the expression of p53, TGF-beta1 and alpha-SMA."
"The level of p53 is suppressed by individual p53 siRNAs were also verified by Western blotting (XREF_SUPPLEMENTARY)."
"It has been proposed that ARF is expressed only when an E2F signaling threshold is exceeded following oncogenic activation. The main activity of ARF is its ability to bind to p53 inhibitors and to control ribosome biogenesis. Human double minute (HDM2) [mouse double minute 2 (Mdm2) in mouse] and ARF protein binding 1 (BP1)/Mule are two specific E3 ubiquitin ligases that mediate p53 degradation through ubiquitination."
"Initial studies showed that p53 siRNA decreased p53 expression by more than 98% in human FLS."
"Addition of p53 targeting siRNA decreased p53 protein expression by 50% within 12 hours and 80% by 24 hours, compared vehicle treated controls (p < = 0.005) (XREF_FIG)."
"p53 knowdown by p53-siRNA transfection inMCF7 cells significantly reduced p53 expression and increased MCF7 cell proliferation."
"Moreover, the p53 signature identified a subset of aggressive tumors absent of sequence mutations in p53 yet exhibiting expression characteristics consistent with p53 deficiency because of attenuated p53 transcript levels."
"Inhibition of p53 expression by p53 siRNA significantly increased cell survival in all treatment groups (p < 0.001) (XREF_FIG)."
"The downregulation of p53 results in an increase in the expression of miR-1228; in turn, miR-1228 targets and negatively regulates p53 expression, resulting in a forward feedback loop of p53/miR-1228/p53."
"Akt (PKB) directly phosphorylates multiple protein targets of relevance to apoptosis (Figure 2B), suppressing cell death clearly within the intrinsic pathway (e.g., BAD inactivation, human caspase-9 suppression) and possibly also the extrinsic pathway (e.g., FasL expression) in some types of cells."
"PDAC was initiated by pancreas restricted Cre-recombinase (Pdx1-Cre) expression in Kras LSL-G12D/+; p53 loxP and loxP (KP) mice to induce mutant Kras G12D expression and loss of p53."
"Treatment of HKC with 75 mJ/cm 2 UVB strongly induced p53 protein levels at 8 h. Knockdown of p53 not only blocked this induction, but also suppressed p53 protein levels below the pre-UVB treatment baseline (XREF_FIG)."
"The restricted pattern of p53 up-regulation seen following the loss of Apc was contrary to expectation, given active Wnt signalling is reported to promote p53 transcription [XREF_BIBR]."
"In addition, p53 down-regulation reduced the protein levels of p53, p-p53, and p21."
"Truncation mutations in TP53 reduce TP53 RNA expression."
"The inhibition of p53 expression by a p53 antisense oligodeoxynucleotide lead to the significant decrease of formation of mature macrophages from U 937 cells in the presence of rhGM-CSF."
"Both p53 expression and the block in thymidine incorporation could be eliminated by p53 antisense oligonucleotides."
"Table 1 Substrates of DNA-PK"
"We now show that p53 and its inhibitor MDM2 (HDM2 in human cells) are together in the nuclei of H7-treated cells and can be co-immunoprecipitated. Despite this association of p53 with the ubiquitin ligase MDM2, ubiquitinated p53 was not detected in H7-treated cells. Furthermore, co-treatment with H7 and the proteosome inhibitor LLnL prevented the accumulation of ubiquitinated p53 that was observed in cells treated solely with LLnL."
"The p53 inhibitor pifithrin-alpha (PFT-alpha) knockdown of the signaling of p53 led vitexin to lose its antitumor effect and inhibited the expression of p53 downstream genes, p2 (WAF1) and Bax."
"The p63 siRNA decreased p63 protein expression by about 50% while the p53 siRNA decreased p53 expression by 80% as quantified from the western blots shown in XREF_FIG."
"Repression of p53 expression by the addition of a lentiviral p53 short-hairpin RNA expression vector increased the frequency of formation of iPS like colonies from 1 (on average) to around 100 per 2 x 10 (4) cells when infected cells were grown on SNL feeder cells."
"However, when expression of the p53 protein in normal HEF cells was suppressed by the antisense oligonucleotide of the p53 gene, growth stimulation was not observed."
"Importantly, although transfection with lentiviral p53 shRNA did not affect cell number in control cells (XREF_FIG), in Brg1 deleted neurospheres, reducing p53 protein levels by p53 shRNA (XREF_FIG) restored cell number (XREF_FIG)."
"p53 +/- mice, that have slightly reduced p53 levels, show the opposite phenotype."
"p53 lentiviral-shRNA transduction moderately suppressed p53 expression in UCD-Mel-N cells (XREF_FIG)."
"Strong nuclear expression of p53 was restricted to mice injected with AAV9-p53 WT and was not inhibited by p53 shRNA (XREF_SUPPLEMENTARY)."
"ATM-mediated phosphorylation of p53 stabilizes this tumor suppressor protein by reducing constitutive interactions with MDM2, which usually promotes the degradation of p53 (Figure 1) (Giaccia and Kastan, 1998; Chin et al., 1999)."
"Reduction of p53 expression by p53 antisense oligonucleotide increases sensitivity of renal cells in culture to hyperosmotic stress caused by NaCl."
"Expression of the tumor suppressor gene product p53 and the cyclin dependent kinase inhibitor p21, which is transcriptionally activated by p53, was investigated and compared with patient survival in a retrospective longitudinal study of 202 cases of endometrial carcinoma."
"At NaCl induced 500 mosmol/kg, apoptosis was rare in the presence of control, nonspecific oligonucleotide but highly prevalent upon addition of p53 antisense oligonucleotide that substantially reduced p53 levels."
"Inhibition of phosphatidylinositol 3-kinase protected cells from the LPA induced reduction of p53, which implicates this signaling pathway in the mechanism of LPA induced loss of p53."
"% UbcH7 is a ubiquitin-conjugating enzyme mediating c-fos degradation, transcription factor NF-kappaB maturation, human papilloma virus-mediated p53 and Myc protein degradation, in vitro."
"Both L11 and L23 have been shown to activate p53 by inhibiting MDM2-mediated p53 suppression."
"In our previous studies [XREF_BIBR], we demonstrated that (a) the basal level of endogenous p53 protein is much higher in mouse Ube4b null MEFs than in parental wild-type MEFs; indicating Ube4b plays a critical role in regulating basal level of p53 in unstressed conditions; (b) overexpression of mouse Ube4b decreased the level of p53 in Mdm2 null MEFs, suggesting that the Ube4b dependent Mdm2 mediated p53 degradation is not absolute."
"CK2-I decreased MDM2-p53 association and p53 ubiquitination to enhance p53 levels."
"Stable transfection of p53 shRNA effectively reduced the protein level of p53."
"To further substantiate the role of p53 in basal promoter activity, p53 expression was knockdown by p53 siRNA transfection of Caco-2 monolayers."
"In either case, alterations in p53 function, diminished p53 protein levels and abnormal karyotypes were evident, irrespective of time or tumour model."
"Here we report that p53 suppressed expression of the cellular FLICE-inhibitory protein (FLIP) that potentially blocks apoptotic signaling in human colon cancer cell lines expressing mutated and wild-type p53."
"Furthermore, by coimmunoprecipitaton and cotransfection assays, we found that PTEN physically binds p53 in vitro as well as in vivo. Binding of PTEN to p53 attenuated MDM2-mediated p53 inhibition."
"The mRNA level of p53 was greatly reduced by the p53 shRNA lentivirus, while the expression of Tet1, but not Tet2 or Tet3, was significantly increased (P < 0.05, unpaired, two tailed Student 's t-tests; XREF_FIG)."
"As anticipated, p53 siRNA reduced p53 expression in SNU-668 cells (XREF_FIG)."
"The transient p53 pulse mode can prevent the p53 protein level from being over-activated, allowing cells to recover from DNA damage."
"By targeting the MDM2-p53 interaction in wild type p53 tumors, the p53 levels can be increased and the cytotoxic response to CDDP might be improved."
"to elucidate the role of nonactive JNK2 in regulating p53 stability the amount of p53-JNK complex was inversely correlated with the p53 level a peptide corresponding to the JNK binding site on p53 efficiently blocked ubiquitination of p53"
"Replacement of p53 3 ' UTR with a commonly used SV40pA greatly reduced p53 reporter expression in the proliferating compartments, suggesting a general role of the 3 ' UTR as a positive regulatory elements in supporting p53 expression."
"Wild-type p53 protein is rapidly degraded via the ubiquitin-proteasome system, resulting in low p53 protein expression."
"Since it has been shown that aspirin, at very high concentration (5 mM) reduced the phosphorylation of STAT3 [XREF_BIBR] and that activated STAT3 binds to the TP53 gene promoter repressing the transcription of TP53 mRNA [XREF_BIBR], we first evaluated the transcription level of TP53 mRNA in the NCM460 and HepG2 cells by Real-time RT-PCR analysis after exposure to progressive concentrations of aspirin."
"In the present study, an immunohistochemical assay revealed that in a model of CCl 4 -induced hepatic fibrosis, Ad-p53 significantly decreased the positive expression of TGF-beta1 and alpha-SMA, and increased the positive expression of p53 compared with the normal saline group."
"In addition, treatment of cells with the PKC activator phorbol ester stimulated the ubiquitination of p53 and reduced its ability to accumulate after stress. H7 did not induce the phosphorylation of human p53 on Ser-15 (Ser-18 in mouse protein), a modification that occurs in response to DNA damage and leads to the release of MDM2 and to transactivation by p53"
"In addition, knockdown of p53 expression by p53 siRNA significantly inhibited the protein level of Fas and CD95, PUMA, cleaved caspase-8 and cleaved caspase-3 (XREF_FIG), cell growth-inhibitory effects (XREF_FIG), and apoptosis (XREF_FIG) after treatment with ESE in HCT 116 cells."
"They reported that overexpression of miR-504 decreases p53 protein levels and functions in cells, including p53 transcriptional activity, p53 mediated apoptosis and cell cycle arrest in response to stress."
"Moreover, nutlin-3a-mediated augmentation of p53 inhibited the mTOR pathways but metformin did not influence p53 levels without nutlin-3a."
"Thus, the expression of p53 was not significantly decreased by BCL6 and repression of p53 by BCL6 is not conserved in mouse B cells."
"p19ARF antagonizes the ability of mdm2 to degrade p53, leading to p53 stabilization (p19ARF = CDKN2A)"
"We report here that enforced Bcl-2 expression in MCF7 cells stabilizes p53, induces phosphorylation of p53 serine 15 (p53pSer15) and inhibits MCF7 cell growth. Bcl-2-positive MCF7 cells proliferate slower than those of Bcl-2 negative."
"Transfection of the TP53 siRNA into primary T cells reduced TP53 expression by ~ 50% (XREF_FIG)."
"Alternative reading frame protein (ARF; known as p14 ARF in humans or p19 ARF in mice) is involved in the p53 tumor-suppressor pathway in which ARF inhibits the ubiquitin protein ligase Mdm2 (or HDM2), and leads to stabilization and elevated levels of p53."
"PML-RAR causes deacetylation and degradation of p53, resulting in repression of p53 transcriptional activity"
"Major deletions in the gene encoding the p53 tumor antigen cause lack of p53 expression in HL-60 cells."
"Importantly, impaired p53 mediated autoregulation of p53 transcription by inducible interfering RNA results in aberrant cell cycle regulation and suppression of p53 mediated apoptosis."
"The complex of E6-AP and E6 specifically interacts with p53 and mediates ubiquitination of p53 in concert with the E1 ubiquitin-activating enzyme and the E2 ubiquitin-conjugating enzyme UbcH5."
"Additionally, p53 targeted shRNA reduced the level of p53 protein expression in CAL-27, SCC-15 and Tca8113 cells by 70.5 +/-2.6, 70.8 +/-2.0 and 71.8 +/-1.9%, respectively (P < 0.05, n = 3)."
"The p53 specific shRNA reduced p53 levels by 80-90%, and these p53 knockdown cells were also significantly less sensitive to both Nutlin-3a- and KPT-185-induced apoptosis (i.e., P < 0.05 in drug specific annexin V induction at all concentrations examined; Fig."
"Interestingly, p53 gene silencing did not cause any significant change in the UV-50-induced p53 protein level (lane 6), suggesting that p53 might not transcriptionally regulate TIGAR gene at high doses of cellular stress."
"The majority of human tumors bear inactive p53 or cellular factors that down-regulate the expression and activity of the p53 network."
"NAD (P) H : quinone oxidoreductase 1 (NQO1) seems to stabilize both p53 and p73, inhibition of which reduces the levels of p53 and p73."
"The p53 specific shRNA reduced p53 levels by 80 to 90%, and these p53 knockdown cells were also significantly less sensitive to both Nutlin-3a and KPT-185 induced apoptosis (i.e., P < 0.05 in drug specific annexin V induction at all concentrations examined, XREF_FIG), suggesting that both the MDM2 inhibitor Nutlin-3a and the XPO1 inhibitor KPT-185 activate p53 mediated signaling to induce apoptosis in MCL cells."
"In addition, MDM2 mediated p53 degradation causes low p53 levels in the absence of p19Arf, thus preventing cell cycle arrest and apoptosis [XREF_BIBR]."
"MDM2 is an E3 ubiquitin ligase which mediates ubiquitylation and proteasome-dependent degradation of the p53 tumor suppressor protein"
"The loss of heterozygosity by p53 gene and the expression of p53 protein have been studied in cancerous pulmonary tissues and congenital cystic adenomatoid malformation by molecular-biologic and immunohistochemial methods."
"Western blot analysis revealed that p53 specific short hairpin RNA reduced p53 levels by 84% (XREF_FIG)."
"Moreover, the binding of beta-arrestin 2 to Mdm2 suppressed the self-ubiquitination of Mdm2 and consequently reduced the Mdm2-mediated p53 degradation and ubiquitination. Further experiments revealed that overexpression of beta-arrestin 2 enhanced the p53-mediated apoptosis while suppression of endogenous beta-arrestin 2 expression by RNA interference technology considerably attenuated the p53-mediated apoptosis"
"Here we show that the simultaneous transient expression of E1B 55-kDa and E4 34-kDa proteins is sufficient to drastically shorten the intracellular half-life of p53, leading to strongly reduced steady-state p53 levels."
"Overexpression of miR-504 decreases p53 protein levels and functions in cells, including p53 transcriptional activity, p53 mediated apoptosis and cell cycle arrest in response to stress, and furthermore, promotes tumorigenecity of cells in vivo."
"The abundance of an essential downstream effecter of this pathway, the tumor suppressor protein p53, is tightly regulated by controlled degradation through COP1 and other E3 ubiquitin ligases, such as MDM2 and Pirh2;"
"3-NP upregulated the expression of tumor suppressor protein 53 (p53) and its target genes including Bax, p53 upregulated modulator of apoptosis (PUMA) and damage regulated autophagy modulator (DRAM)."
"Rp or Zp was activated by MNNG (1 mug/ml for 24 h) at levels about 2.6-fold or 1.1-fold higher than the solvent control, but was reduced to 1.0-fold or 0.9-fold when the expression of p53 was abrogated by p53 siRNA in TW01 cells (XREF_FIG)."
"Furthermore, the pro apoptotic action of VB was obscured by a p53 specific inhibitor, which restored protein levels of p-p53 (Ser46), p53, Bax, and Bcl-2 to the untreated status."
"Min et al. showed that one p53 target gene, phosphatase of regenerating liver 1 (PRL-1), that is overexpressed in a variety of cancers through an unknown mechanism, strongly down-regulated p53 levels and inhibited p53 mediated apoptosis by inducing MDM2 phosphorylation through Akt signaling, which forms another feedback loop contributing to HCC development."
"from full text - MdmX blocks p53 transactivation and degradation ...MdmX is capable of associating with p53"
"We exploited the conditional nature of the XTR system, to determine whether somatic recombination of p53 XTR and XTR to p53 TR/TR would inactivate p53 expression and lead to rapid onset of lymphoma in Emu-Myc transgenic mice."
"28 Ischemin (compound 2, K d = 19 muM) inhibited p53 induced p21 activation in a luciferase reporter gene assay (IC 50 = 5 muM) and down-regulated p53 target gene expression under oxidative stress conditions."
"Transfection of p53 siRNA decreased p53 protein expression in both cell lines."
"The inhibition of p53 expression by the p53 antisense oligonucleotide not only blocked the expression of Bax but also partially suppressed the increased GAPDH mRNA and protein levels."
"Finally, the uba domain is necessary for the ability of full-length hPLIC-2 to interfere with the ubiquitin-mediated proteolysis of p53."
"Our results show clearly that changes in the intrinsic thermodynamic stability of p53 reduce the level of folded and hence functional p53 substantially in E. coli, and provide insights into the correlation between protein instability and disease at the cellular level."
"Two p53 specific small interfering RNA (siRNA) oligos (si-p53-1 and si-p53-2) targeting different mRNA regions of p53 were used to effectively repress p53 expression in HCT116 (p53 +/+) cells, which resulted in a corresponding 50-60% reduction in ERAP1 mRNA (XREF_FIG) and protein (XREF_FIG) levels."
"Using the proteasome-specific inhibitors, MG132 and lactacystin, we show that the p53, the cdk inhibitors p21 and p27, and cyclin A are degraded by the ubiquitin-proteasome pathway in human osteosarcoma cells."
"The results have shown that As-ODNs targeting mRNA of p53 and p21 downregulate radiation induced expression of p53 and p21 (WAF1 and CIP1)."
"Ubiquitination and degradation of p53 is dependent on MDM2...stimulates"
"Furthermore, silencing of endogenous RBEL1A significantly enhanced the formation of p53 oligomeric complex following ultraviolet radiation mediated DNA damage and RBEL1A knockdown also enhanced expression of p53 target genes."
"p53 gene specific antisense oligodeoxynucleotides strongly inhibited expression of p53 gene in T lymphocytes, causing suppression of ConA induced cell proliferation."
"p53 specific shRNA reduced p53 basal levels by more than 90% in both OCI-AML-3 and MOLM-13 cells (XREF_FIG and XREF_SUPPLEMENTARY)."
"The life history of cancer cells encompasses a series of genetic missteps in which normal cells are progressively transformed into tumor cells that invade surrounding tissues and become malignant. Most prominent among the regulators disrupted in cancer cells are two tumor suppressors, the retinoblastoma protein (RB) and the p53 transcription factor. Here, we discuss interconnecting signaling pathways controlled by RB and p53, attempting to explain their potentially universal involvement in the etiology of cancer. Pinpointing the various ways by which the functions of RB and p53 are subverted in individual tumors should provide a rational basis for developing more refined tumor-specific therapies."
"In contrast, Cr (VI) decreases p53 degradation, increasing the levels of active p53, likely through the production of reactive oxygen species [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
"p53 inhibits cell cycle progression and DNA damaging cytostatics induce p53 protein expression, indicating that p53 responds to DNA damage."
"To investigate whether epithelial cells acquire the ability to suppress p53 induction in adjacent stromal cells in the course of neoplastic transformation, we took advantage of normal primary human bronchial epithelial cells immortalized with human telomerase (NHBET) and their in vitro transformed derivatives stably expressing mutant H-Ras and short-hairpin RNA specific for p53, which strongly downregulates their p53 protein levels (XREF_FIG)."
"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."
"The COP9 signalosome (CSN) purified from human erythrocytes possesses kinase activity that phosphorylates proteins such as c-Jun and p53 with consequence for their ubiquitin (Ub)-dependent degradation."
"In vitro sumoylation of Mdm2 abrogates its self-ubiquitination and increases its ubiquitin ligase activity toward p53"
"As shown in Figure XREF_FIG, knockdown of p53 protein expression by p53 shRNA-1 (P1) or p53 shRNA-2 (P2) resulted in increased expression of FoxM1 protein in both A2780 and NCI-H23 cells as compared to NTC."
"Transfection of p53 siRNA nearly completely abolished basal p53 expression and prevented TMZ- and fotemustine induced p53 up-regulation as well as p53 (Ser15) phosphorylation (XREF_FIG)."
"# Ariadne: Our results indicate that NQO1 regulates degradation of p53 in the proteasomes by a mechanism that is independent of both Mdm-2 and ubiquitin. [Regulation] # Ariadne: Inhibition of NQO1 Activity Induces Mdm-2-Independent p53 Degradation That Is Blocked by p14 ARF . [Regulation]"
"When the expression level of p53 was downregulated by p53 siRNA, luciferase activity was also significantly inhibited."
"TP53 siRNA efficiently inhibited endogenous TP53 expression in UM-SCC-11B and 22A over 96 hours (XREF_FIG, XREF_SUPPLEMENTARY)."
"Exploration of the mechanism showed that miR-138 directly targeted the 3 ' untranslated region (UTR) of p53, significantly decreasing the expression of p53 and its downstream genes."
"However, we also uncover a regulatory pathway whereby suppression of p53 Ser (15) phosphorylation is associated with enhanced phosphorylation at Ser (46), increased p53 protein levels, and induction of Noxa expression."
"Phosphorylation of MDM2 at S166 and S186 by p-AKT can activate its ubiquitin ligase activity toward p53 23 causing reduced expression of p53."
"We found that p53-shRNA and pSK-H 1-Pu-X was able to inhibit the endogenous p53 expression, with over 80% suppression compared to the vector control."
"Arsenite alone or in combination with hyperthermia selectively sensitized TP53 expressing cells to cisplatin [XREF_BIBR]; arsenite sensitization effect was abrogated by TP53 siRNA."
"Western blot revealed that the p53-shRNA successfully suppressed expression of the endogenous p53 in MCF-7 cells."
"Mdm2 binds to p53 and promotes its degradation"
"Interestingly, the TP53 transcripts slightly increased after trametinib treatment, suggesting MAPK activity inhibited TP53 transcription, which was reversed by trametinib in WM35."
"Knockdown of p53 expression by p53 shRNA significantly blocked docetaxel induced apoptotic cell death compared to the vector control, while overexpression of wild-type p53 in DU145 cells increased their sensitivity to docetaxel."
"The effects of combining a phosphorothioate oligonucleotide OL (1) p53, which transiently down-regulates p53 levels, with an anthracycline, Idarubicin, on the growth of wild-type p53 WMN gene expressing lymphoma cells was evaluated."
"The induction of p53 can be an effective means to block tumor progression; however, in our tumor eradication experiments, p53 expression was suppressed in the induced gliomas by p53-shRNA."
"Treatment of p53 transfected cells under anoikis conditions reduced exogenous p53 levels (XREF_FIG, lanes 4 and 5)."
"We also indentified an E-box located at p53 promoter which is required for Twist to inhibit p53 expression."