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

p53 is a cellular protein whose expression plays a crucial role in the regulation of cell proliferation and of neoplastic processes. p53 mRNA levels in mouse fibroblasts can be elevated in response to TPA and to serum stimulation. The promoter region of the p53 gene contains a conserved element which is highly homologous to the consensus AP1 binding site (7/8 matching bases). This AP1-like site, denoted the PF1 site, confers upon a heterologous promoter ability to respond to elevated expression of c-jun. Furthermore, the PF1 site binds protein(s) in a specific and serum-induced manner. Unexpectedly, this factor is most probably not AP1, as evident from the inability of an authentic AP1 site to compete the binding efficiently, as well as from the failure of purified AP1 to bind to the PF1 site. Hence, PF1 may be a novel AP1-related transcription factor. In addition, the 5' region of the p53 gene also contains an NF1 binding site, whose location suggests a possible regulatory role.
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PMID:Protein-binding elements in the promoter region of the mouse p53 gene. 221 54

We have isolated, sequenced, and characterized a human MN/CA9 gene. This gene is a novel member of the carbonic anhydrase (CA) family, which codes for widely distributed catalysts of the reversible conversion of carbon dioxide to carbonic acid. So far, MN/CA IX is the only tumor-associated CA isoenzyme. The entire genomic sequence of MN/CA9, including the 5'-flanking region, encompasses 10.9 kb. The coding sequence is divided into 11 exons, whose organization and relationships to predicted protein domains suggest that the gene arose by exon shuffling. Exon 1 encodes a signal peptide and a proteoglycan-related region. Exons 2-8 code for a CA domain with a highly conserved active site. The exon/intron pattern of the CA coding region is similar but not identical to other described animal kingdom alpha-CA genes. Exons 10 and 11 encode a transmembrane anchor and an intracytoplasmic tail, respectively. We have also determined the transcription initiation and termination sites by RNase protection assay and analyzed the 3. 5-kb region upstream of the MN/CA9 gene. Sequence of the proximate 5' end of the flanking region shows extensive homology to the long terminal repeats of HERV-K endogenous retroviruses. The putative MN/CA9 promoter immediately preceding the transcription start site does not possess a TATA box, but contains consensus sequences for the AP1, AP2, p53, and Inr transcription factors. This study will allow further investigations of the molecular events regulating expression of MN/CA IX as well as elucidation of its biological function.
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PMID:Human MN/CA9 gene, a novel member of the carbonic anhydrase family: structure and exon to protein domain relationships. 866 Oct 7

DNA sequencing of intron 4 of the p53 gene from seven cutaneous melanoma cell lines showed an absence of mutations. However, both control and melanoma cell lines sequences were different from the reference source obtained from GenBank databank (accession No. X54156). Base pairs 101 and 689 were determined to be T (instead of A) and C (instead of G). Also, an additional C was not detected at position 371. Comparative analysis with p53 DNA-binding sequences, a sequence recognized by a p53 intron 4-binding protein and consensus sequences recognized by transcription factors demonstrated that intron 4 contains putative sequences for NF-kappa B, SP1, AP1 and TFIID binding. Binding of transcription factors could be one of the mechanisms by which intron 4 modulates human p53 expression.
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PMID:Analysis of intron 4 of the p53 gene in human cutaneous melanoma. 891 63

The amelogenins are found uniquely in enamel, where they constitute the predominant class of secreted matrix proteins and where they play a fundamental role in normal enamel formation. To better understand the high level of tissue-specific expression, we cloned the bovine X and Y chromosomal amelogenin genes and the murine amelogenin gene and determined the DNA sequences for the regions upstream of the transcription start sites. We observed segments of strong homology among species, and identified consensus sequences for the binding of various transcription factors, including the glucocorticoid receptor, AP1, RXR and p53. Although specific sis-elements conferring enhanced transcription have not yet been identified, elements have been localized that have silencing effect in non-ameloblast cells. Conserved sequences are likely to be involved in tissue-specific expression. Transgenic mouse studies have shown that 3.5 kb of upstream region is sufficient but 900 bp is insufficient for specific expression in vivo. Alternative splicing of the primary transcript is an effective mechanism for generating molecular heterogeneity. Amelogenin genes contain seven exons, and exons 3, 4, 5 and most of 6 can be deleted by alternative splicing. However, the pattern of exon splicing varies according to the species, and skipping of bovine exon 3 appears to be developmentally regulated. It will be important to determine whether the relative amounts of translation products differ among species as do the mRNAs, and to correlate the various protein structures with function. These findings also suggest that the regulation of amelogenin gene expression is complex and takes place at several levels.
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PMID:Regulation of amelogenin gene expression. 918 25

The products of the p53 and CBP/p300 genes have been individually implicated in control of cell growth and regulation of transcription. p53 is known to act as a positive and negative regulator of gene expression. Here we show that p53, in both wild-type and mutant conformation, forms a specific protein complex with p300. However, in its wild-type but not mutant conformation, p53 inhibits a promoter containing the DNA-binding sequences for the transcription factor AP1, in a p300-dependent manner. p300 stimulates the transcriptional activity of p53 on p53-regulated promoters, and it enhances the responsiveness to a physiological upstream modulator of p53 function, ionizing radiation. A dominant negative form of p300 prevents transcriptional activation by p53, and it counteracts p53-mediated G1 arrest and apoptosis. The data implicate p300 as an important component of p53-signaling, thus providing new insight into the mechanisms of cellular proliferation.
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PMID:Recruitment of p300/CBP in p53-dependent signal pathways. 921 39

To identify features of the human thrombospondin 2 gene (THBS2) important for regulation of expression, the sequences of 5 kb of the promoter/5' flank and 3 kb of transcribed and intronic DNA were determined. Two repetitive sequences were found: an MLT1c element located 2.2 kb 5' of exon 1 and, further 5', 1.8 kb of a Tigger1 element. Putative transcription factor binding sites that might be significant for THBS2 regulation included p53, NF-kappaB, Spl, Myc-CF1, NF-Y, CF1, AP1, and GATA sites. Alignment of the promoter/5' flank sequence with the mouse Thbs2 promoter revealed 78% identity for a 450 bp region immediately upstream from the mouse transcription start site. No significant homology was detected between the human thrombospondin 2 and thrombospondin 1 promoters. Comparison of the THBS2 genomic and cDNA sequences revealed that, in contrast to Thbs2, exon 1 is divided into exons 1A and 1B by a small (93 bp) intron. The transcription start site was investigated by a PCR procedure and by 5' RACE, and yielded a size for exon 1A of at least 186 bp. Tissue-specific differences in transcription start sites were found, with transcript lengths in the order: fetal lung > adult lung > fetal brain. These results suggest that tissue-specific differences in expression of the THBS2 gene may be determined, in part, by selection of the transcription start site and resulting differences in the 5' untranslated region.
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PMID:Analysis of the promoter and transcription start sites of the human thrombospondin 2 gene (THBS2). 924 61

Ro 41-5253 is a RARalpha-selective antagonist that binds RARalpha but does not induce transcriptional activation and does not influence RAR/RXR heterodimerization and DNA binding. This retinoid inhibits proliferation and induces apoptosis in MCF-7 and ZR-75.1 estrogen-receptor-positive breast-carcinoma cells in a dose-dependent way. The anti-proliferative effect is more evident in ZR-75.1 cells than in MCF-7 cells and is probably mediated by anti-AP1 activity, a mechanism known to be implied in the action of several retinoids. In the induction of apoptosis also ZR-75.1 cells are more sensitive to treatment with Ro 41-5253 than MCF-7 cells. In ZR-75.1 cells an apoptotic/hypodiploid DNA peak is already evident after 2 days of incubation, whereas in MCF-7 cells it appears only after 4 days. The highest percentage of apoptotic cells, for both cell lines, is reached after 6 days of treatment. The apoptosis pathway is p53-independent and bcl-2 downregulation seems to be correlated with an increase in TGF-beta1 protein. The MDA-MB-231 estrogen-receptor-negative cell line is poorly responsive to Ro 41-5253 treatment, both in terms of proliferation inhibition and apoptosis induction. Ro 41-5253 has proliferation-inhibiting and apoptosis-inducing properties that are not mediated by transcriptional activation from retinoic-acid response elements. This retinoid antagonist seems to be a compound that exerts an anti-tumor activity but does not induce the toxic side effects of retinoids and might, therefore, be considered as a candidate for cancer therapy.
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PMID:RARalpha antagonist Ro 41-5253 inhibits proliferation and induces apoptosis in breast-cancer cell lines. 972 98

The adult rat liver is normally in a state of growth arrest. However, cell loss such as partial hepatectomy can induce the proliferation of the hepatocytes. Early after partial hepatectomy, the concentration of p53 mRNA increases during the prereplicative phase. In this study, we identified the cis-regulatory element involved in the induced transcription of the rat p53 gene by DNase I footprinting assay. This element had a partial homology to the AP1 recognition motif, but the competition study with AP1 oligonucleotide showed that this element was not the AP1 recognition motif. The molecular weight of the binding protein to this motif was determined as 39 kDa by southwestern blotting analysis. In vitro transcription assay with the competitor containing the binding motif showed that the 39 kDa protein binding to the element was required for the induced transcription of the rat p53 gene during the liver regeneration.
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PMID:Transcription of the rat p53 gene is induced by a 39kDa protein binding to the p53 promoter region during the liver regeneration. 984 38

In vitro studies have shown that ionizing radiation can cause increases in some cytokine mRNA levels and activation of the nuclear NF-kappa B and/or AP1 transcription factors which have been implicated in the transcriptional regulation of many cytokine genes. Thus, radiation-induced upregulation of cytokine mRNAs appeared to be in part a direct consequence of transcription factor activation. To test this in vitro model in vivo, the effects of whole-body X-irradiation (0-10 Gy) on cytokine and other gene mRNA levels have been examined in mice. Increases and decreases in cytokine mRNA levels were detected in tissues which underwent an early wave of apoptosis (bone marrow and/or spleen), but not in more radioresistant tissues (kidney, liver, brain, and heart). Some mouse strain-specific differences were observed, but none of the changes in mRNA level was detected in p53-/- mice. As activation of the NF-kappa B and AP1 transcription factors was not detected in early-(spleen) or late-(liver) responding tissues in 10 Gy X-irradiated p53+/+ mice in vivo, it is concluded that the modulation of cytokine gene expression in vivo is p53-dependent and indirectly associated with apoptosis.
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PMID:p53-dependent X-ray-induced modulation of cytokine mRNA levels in vivo. 987 36

The rat p53 promoter has several potential transcription factor-recognition motifs. They include NF1-like, bHLH family, and AP1-like proteins binding sites. The binding protein to NF1-like motif was previously identified. The protein has about 40kDa of molecular mass, which is smaller than that of NF1. Anti-NF1 polyclonal antibody does not recognize the protein. In this study, we isolated the 40kDa protein by sequence-specific DNA affinity chromatography. The isolated protein was assayed by DNase I footprinting analysis. To determine the transactivation effect of the protein, in vitro transcription with the purified 40kDa protein was carried out. After the addition of the purified 40kDa protein into the transcription reaction mixture, the transcription level of the p53 promoter was increased. This suggests that the 40 kDa NF1-like protein is a transcription activator for the rat p53 gene.
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PMID:In vitro transcription assay with the purified 40kDa NF1-like protein binding to the rat p53 promoter. 1020 79


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