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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been reported recently that the wild-type p53 gene product can positively regulate the expression of a test gene adjacent to the enhancer-promoter elements of the murine muscle-specific creatine kinase (MCK) gene. This discussion reports the identification of a wild-type p53 protein-specific DNA-binding element located within the p53-responsive region of the MCK enhancer-promoter element. This p53 protein/DNA-binding element has been defined by DNase I footprint analysis, which identified a 50-bp region. This 50-bp sequence was sufficient to confer wild-type p53 responsiveness on a heterologous minimal promoter. The mutant forms of p53 protein are much less capable of stimulating this DNA element. This study has identified the first example of a naturally occurring wild-type p53-specific DNA-binding element that is able to mediate positive regulation of a test gene. The results suggest a biological function in gene regulation for the wild-type p53 protein that is lost or altered in the mutant p53 proteins.
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PMID:Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element. 162 22

p53 is an antioncogene that is defective or absent in a large number of human tumors. Its function in normal cells is not known. We show that co-transfection of mouse p53 with muscle-specific creatine kinase-chloramphenicol acetyltransferase reporter gene, containing 3.3 kilobase of upstream control sequence for the muscle-specific creatine kinase gene, results in a 10- to 80-fold activation. The p53 responsive element maps to a region distinguished from the known MyoD binding region. Identification of a p53 responsive element should allow a more focused analysis of the effects of p53 in controlling gene activity.
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PMID:The MCK enhancer contains a p53 responsive element. 164 9

Transcriptional activation by p53 is dependent on the presence of a specific p53 binding site within control sequences of the target gene. One such target gene is the mouse muscle-specific creatine kinase (MCK) gene, which contains a p53 binding site between promoter residues -3182 and -3133 relative to the transcription start site. This DNA sequence is reported to be sufficient to confer p53-dependent activation on the MCK promoter. In contrast to this finding, evidence from promoter deletion studies suggests that sequences in the MCK promoter other than this p53 binding site also permit p53-dependent activation. To investigate this possibility, we have further examined sequences in the MCK promoter required for transcriptional activation by mouse p53. We report here identification of a second p53-responsive sequence within the MCK promoter. This novel sequence is situated between residues -177 and -81, and can confer p53-dependent, position- and orientation-independent activation on a heterologous promoter. Moreover, this sequence can specifically bind mouse and human p53. By promoter deletion studies, we provide evidence that these two elements cooperate to provide high-level, p53-dependent activation of the MCK promoter.
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PMID:p53-dependent activation of the mouse MCK gene promoter: identification of a novel p53-responsive sequence and evidence for cooperation between distinct p53 binding sites. 748 58

Creatine kinase (CK; EC 2.7.3.2) isoenzymes and their substrates have an important function in cellular energy generation and utilization. The brain isoform (CK-BB) has been implicated in cellular transformation processes involving the oncogenic products of the Ela virus and the p53 tumor suppressor gene. Cyclocreatine, an analogue of creatine, has been previously shown to inhibit the growth of a broad spectrum of cancer cells derived from solid tumors. Results reported herein indicate an increased level of creatine kinase activity in human prostate carcinoma cell lines and inhibitory effects of cyclocreatine alone and in combination with adriamycin on the growth of these cells in vitro and in vivo, in immune-deprived mice. Our results suggest the possible use of cyclocreatine in the treatment of prostatic carcinoma.
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PMID:Antiproliferative effects of cyclocreatine on human prostatic carcinoma cells. 765 18

The p53 mutant Val135 is widely considered to have a wild-type (wt) phenotype at 32.5 degrees C, but not at 37 degrees C. The ability of wt murine p53 and its Val135 mutant to modulate transcription from the muscle-specific creatine kinase promoter (-3.3 kb pMCK), from a reporter construct containing two copies of the p53-binding DNA element from within MCK (p50-2), and from the interleukin-6 (IL-6) promoter (pIC225) was evaluated in transient transfection experiments in CV1 and HeLa cells. In CV1 cells, wt p53 was confirmed to activate the pMCK and p50-2 reporters, but to repress the IL-6 promoter. However, although in these cells p53 Val135 had the expected wt-like phenotype with respect to activation of the p50-2 reporter at 32.5 degrees C (32.5 degrees C > 37 degrees C), this mutant had little effect on expression from pMCK at either temperature, and activated rather than repressed the IL-6 promoter at 32.5 degrees C. In HeLa cells, although wt p53 activated p50-2 but repressed the MCK and IL-6 promoters, p53 Val135 activated all three reporters. Unexpectedly, in these cells the upregulation of p50-2 and pIC225 was basically temperature-independent, and that of pMCK was inversely ts (37 degrees C > 32.5 degrees C). The novel ts properties of p53 Val135 show that this mutant is not always wt-like at 32.5 degrees C but exhibits strong cell-type and promoter-dependent differences in its ts phenotype for transcriptional modulation.
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PMID:Cell-type- and promoter-dependent ts phenotype of p53 Val135. 824 45

Our group has developed more than 600 DNA markers to build a map of the canine genome. Of these markers, 125 correspond to genes (anchor loci). Here we report the first six autosomal genes assigned to canine chromosomes by fluorescence in situ hybridization (FISH), using cosmid DNA: adenine phosphoribosyl transferase on Chromosome (Chr) 3; creatine kinase muscle type on Chr 4; pyruvate kinase liver and red blood cell type on Chr 2; and colony-stimulating factor-1 receptor, glucose transporter protein-2, and tumor protein p53 on Chr 5. These assignments are based on the karyotype proposed by Stone and associates (Genome 34, 407, 1991) using high-resolution techniques. In addition, we have assigned the Menkes gene to the X Chr of the dog.
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PMID:Chromosomal assignment of seven genes on canine chromosomes by fluorescence in situ hybridization. 866 96

In this pharmacokinetic and dose-escalation study of the carboplatin/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combination, patients were randomly assigned to receive paclitaxel either as a 1-hour or a 3-hour infusion. The 1-hour infusion was feasible, with maximum tolerated doses similar to those previously reported for a 3-hour infusion. Using patients' age, height, plasma creatinine, and plasma creatine kinase provided an improved estimate of the glomerular filtration rate compared with the more traditional creatinine-based formulas according to population analysis of data derived from glomerular filtration rate estimates performed by an isotope method. Studies of the p53 gene sequence of ovarian tumors at diagnosis suggest that p53 mutations are a potent predictor of response to subsequent treatment with carboplatin.
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PMID:Carboplatin and paclitaxel, alone and in combination: dose escalation, measurement of renal function, and role of the p53 tumor suppressor gene. 1019 Jul 88

Protein sulfhydryl groups can undergo reversible oxidation reactions in response to reactive oxygen and reactive nitrogen species. Sensitive detection of sulfhydryl group oxidation in specific proteins is required to further our understanding of protein redox changes in biological systems. In general, to detect reversible oxidation reactions the oxidized sulfur atom is reduced to a sulfhydryl group followed by a reaction with a quantifiable agent. Our aim was to develop a sensitive method to detect reversibly oxidized protein sulfhydryl groups in a Western blot format. Conjugation of methoxypolyethylene glycol-maleimide (MAL-PEG) to protein sulfhydryl groups was optimized. Once MAL-PEG forms a covalent bond with the protein, the MAL-PEG-protein conjugate can be detected as a band shift by western analysis. The efficiency of MAL-PEG conjugation to protein was determined with creatine kinase. MAL-PEG conjugated to approximately 100% of the available sulfhydryl groups on creatine kinase within 30 min. Band shift detection sensitivity was measured using the redox-regulated protein p53. MAL-PEG conjugation coupled to western analysis detected a minimum of 0.23 pmol of oxidized p53. The MAL-PEG conjugation method described in this communication can be used to assess the reversible sulfhydryl oxidation status of proteins for which antibodies suitable for western analysis are available.
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PMID:Development of a sensitive assay to detect reversibly oxidized protein cysteine sulfhydryl groups. 1181 84

Previous studies on skeletal muscle differentiation showed that myogenesis is regulated by extracellular signal-regulated kinases (ERK-1/-2) and p38 mitogen activated kinase (MAPK) pathways. Present study shows that c-Jun NH2-terminal protein kinase (JNK) activities were up regulated during skeletal muscle differentiation in rat skeletal muscle L6E9 cells, as determined by Western immunoblot of differentiating cells probed with anti-phospho-JNK antibody. Inhibition of JNK activities by JNK inhibitor II drastically inhibited differentiation as determined by decreased myosin, myogenin expression and creatine kinase activity. The inhibition of the differentiation was regulated by apoptosis as determined by the detection of poly(ADP-ribose) polymerase (PARP) cleavage, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells when JNK activities were inhibited. Apoptosis was accompanied by marked expression and activation of c-Jun and p53 transcription factors. Taken together, our results indicate that basal JNK activities are essential for regulating skeletal muscle differentiation, and inhibition of JNK activation affects myogenesis by apoptosis dependent on c-Jun and p53 transcription factors.
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PMID:Involvement of c-Jun N-terminal kinase activities in skeletal muscle differentiation. 1575 Aug 49

Ischemic cardiovascular disease is a common age-related disease. The p53-dependent cardiac myocyte apoptosis induced by myocardial ischemia/reperfusion (MI/R) is an important feature in the progression of ischemic heart disease. In the present studies, we hypothesized that inhibition of p53-dependent myocyte apoptosis may improve cardiac dysfunction in aged rats after MI/R. A dose (2.2 mg/kg, i.p.) of pifithrin-alpha (PFT), a p53 inhibitor, or saline was administered to 20-month-old male F344 rats, which were subjected to 30 min of myocardial ischemia by ligating the left main coronary artery, followed by release of the ligature and 4 h of reperfusion. Results of our experiments indicate that MI/R induced a significant decrease in cardiac output index (CI) and mean arterial blood pressure (MABP). Administration of PFT to aged rats 40 min before ischemia significantly improved CI and MABP during 3 to 4 h of reperfusion. The improvement of cardiac function was associated with a marked reduction in DNA fragmentation in the area at risk of the heart when compared with aged MI/R rats pretreated with saline. Interestingly, treatment with PFT 10 min after ischemia or 10 min after reperfusion had a similar protective effect on CI and MABP, but this effect did not reach statistical significance when compared with aged MI/R rats pretreated with saline. Treatment with PFT, however, did not influence plasma creatine kinase activity and the number of circulating leukocytes and infiltrated leukocytes in the area at risk of the heart. Moreover, results of Western blot show that pretreatment with PFT significantly attenuated the ratio of Bax to Bcl-2 in the area-at-risk tissue of the heart compared with that of rats pretreated with saline. Our results suggest that pretreatment with PFT significantly improved cardiac function. The mechanism of protective effect of PFT may involve the inhibition of p53 transcriptional function, thereby attenuating the p53/Bax-mediated myocyte apoptosis during the reperfusion period.
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PMID:Pifithrin-alpha attenuates p53-mediated apoptosis and improves cardiac function in response to myocardial ischemia/reperfusion in aged rats. 1711 37


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