Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The finding that in many human tumors there is allelic loss and/or mutations in p53, in combination with recognition that these events may play a role in multi-stage carcinogenesis, has focused considerable interest on this gene. To help keep abreast of this rapidly expanding field, recent experiments on the role and potential regulation of p53 are described: these include discussions of p53 as an anti-proliferative agent, the p53 mutations found in human tumors and tumor cell lines, the conformational states of p53, phosphorylation of p53 by p34cdc2, and signals for the nuclear localization of p53. p53 may act as a transcriptional activator and the specific DNA sequences to which p53 protein binds are also discussed as is the importance of abrogation of p53 function in overcoming cellular senescence.
 ...
PMID:Cellular and molecular advances in elucidating p53 function. 137 32

The cellular phosphoprotein p53 inhibits progression through the mammalian cell cycle. Both p53 alleles are frequently mutated in human tumours, indicating that p53 is a tumour suppressor. Recent studies have suggested that p53 functions as a transcriptional activator, but the significance of this activity in cell-cycle control has not been established. The adenovirus 2 (Ad2) early 1B (E1B) 55K protein binds to p53 in transformed cells and contributes to oncogenic transformation by Ad2 (refs 10-12). Here we report that mutants of E1B 55K and wild-type Ad12 E1B 54K proteins show a strong correlation between their ability to inhibit p53-mediated transcriptional activation and their ability to cooperate with adenovirus E1A protein in the transformation of primary cells. These results indicate that p53 probably inhibits cell cycling by functioning as a transcription factor.
 ...
PMID:Inhibition of p53 transactivation required for transformation by adenovirus early 1B protein. 153 43

Recent efforts have been directed at identifying and characterizing candidate tumor suppressor genes and the activities of oncogenes in primary brain tumors. The p53 gene mapping to region p13 of chromosome 17 has several characteristics as a tumor suppressor gene. The wild-type p53 protein, which is a transcriptional activator, may serve as a barrier to the progression of neoplastic processes, and alterations of p53 are involved in genesis of various cancers including astrocytomas. The NF1 gene, which is responsible for the susceptibility to neurofibromatosis type 1, has recently been isolated. This gene is assumed to play a role in the signal transduction pathway by interacting with the ras gene product. Recent observation revealed that the NF1 gene may regulate the neuronal differentiation, and the alteration in regulation of the NF1 transcript is potentially related to the progression of neuroectodermal tumors. Restriction fragment length polymorphism studies have also shown chromosomal losses associated with chromosome 9, 10 and 17. These losses of genetic material are suspected to involve loci near or at the p53 gene for chromosome 17, and neighboring the interferon genes on chromosome 9. Although no sublocalization of chromosome 10 deletions has been accomplished, all of these loci are thought to harbor tumor suppressor genes. Recent advances in oncogene research have focused on understanding the mechanisms of action of growth factors, growth factor receptors, and their substrates, particularly in glial oncogenesis. Fibroblast growth factor, epidermal growth factor, and their respective receptors are of particular interest. However, the ROS oncogene, which is expressed and rearranged in some glioma cell lines, may not be a critical factor in the development of gliomas.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Pathways of oncogenesis in primary brain tumors. 190

Sera from 39,898 blood donors were tested for HTLV-1 antibodies using two enzyme immunoassays (EIA). Sera testing initially reactive (IR) were retested in duplicate by both EIAs. Sera testing repeatedly reactive (RR) were further tested by two Western blots (WB) and by two radioimmunoprecipitation assays (RIPA). There were 176 (0.44%) EIA IR and 68 (0.17%) RR results. On WBs, 10 of the 68 EIA RR sera demonstrated reactivity to HTLV-1 gag gene-encoded core protein p24, with or without reactivity to other core proteins (p19, p28, p53/55). These ten sera were the only ones demonstrating reactivity on RIPAs to other HTLV-1 gene products - env gene-encoded glycoproteins gp46, gp61/68, or tat gene-encoded HTLV-1 transcriptional activator p40x. These ten sera were interpreted as positive for HTLV-1 antibodies. Of the remaining 58 EIA RR sera, 21 were negative by WBs and RIPAs, 37 sera demonstrated reactivity to various combinations of p19, p28, and p53/55, but not to p24 on WBs. These 37 sera were interpreted as "indeterminate", because they were negative by RIPAs. We conclude that: 1) EIA testing and WB/RIPA verification identified 10 (0.025%) HTLV-1 infected individuals among 39,898 low-risk blood donors; 2) anti-p24 may be a more sensitive and specific indicator of HTLV-1 infection than antibodies to p19, p28, or p53/55; and 3) presently, both WB and RIPA are needed to verify HTLV-1 EIA reactivity.
 ...
PMID:Detection of antibodies to human T-lymphotropic virus type 1 (HTLV-1). 283 83

The gene p53 encodes a transcriptional activator of genes involved in growth arrest, DNA repair and apoptosis. Loss of p53 function contributes to tumour development in vivo. The transcriptional activation function of p53 is inactivated by interaction with the mdm2 gene product. Amplification of mdm2 has been observed in 36% of human sarcomas, indicating that it may represent an alternative mechanism of preventing p53 function in tumour development. To study mdm2 function in vivo, we generated an mdm2 null allele by homologous recombination. Mdm2 null mice are not viable, and further analysis revealed embryonic lethality around implantation. To examine the importance of the interaction of MDM2 with p53 in vivo, we crossed mice heterozygous for mdm2 and p53 and obtained progeny homozygous for both p53 and mdm2 null alleles. Rescue of the mdm2-/- lethality in a p53 null background suggests that a critical in vivo function of MDM2 is the negative regulation of p53 activity.
 ...
PMID:Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. 747 26

The human hepatitis B virus (HBV) HBx protein is a small transcriptional activator that is essential for virus infection. HBx is thought to be involved in viral hepatocarcinogenesis because it promotes tumorigenesis in transgenic mice. HBx activates the RAS-RAF-mitogen-activated protein (MAP) kinase signaling cascade, through which it activates transcription factors AP-1 and NF-kappa B, and stimulates cell DNA synthesis. We show that HBx stimulates cell cycle progression, shortening the emergence of cells from quiescence (G0) and entry into S phase by at least 12 h, and accelerating transit through checkpoint controls at G0/G1 and G2/M. Compared with serum stimulation, HBx was found to strongly increase the rate and level of activation of the cyclin-dependent kinases CDK2 and CDC2, and their respective active association with cyclins E and A or cyclin B. HBx is also shown to override or greatly reduce serum dependence for cell cycle activation. Both HBx and serum were found to require activation of RAS to stimulate cell cycling, but only HBx could shorten checkpoint intervals. HBx therefore stimulates cell proliferation by activating RAS and a second unknown effector, which may be related to its reported ability to induce prolonged activation of JUN or to interact with cellular p53 protein. These data suggest a molecular mechanism by which HBx likely contributes to viral carcinogenesis. By deregulating checkpoint controls, HBx could participate in the selection of cells that are genetically unstable, some of which would accumulate unrepaired transforming mutations.
 ...
PMID:Hepatitis B virus HBx protein deregulates cell cycle checkpoint controls. 747 68

The expression of the 7B2 protein, secreted from a variety of neural and endocrine tissues, increases dramatically in specific neuroendocrine tumors. We have recently shown that human 7B2 can act as a molecular chaperone in the deaggregation of proteins in vitro. In order to identify polypeptides which might bind 7B2 in vivo, the yeast two-hybrid system was employed. Surprisingly, mere covalent linkage of 7B2 to the DNA-binding domains of two yeast transcription activators, Ace1 and Gal4, activates transcription from the ACE1 and GAL4 operon. 7B2's ability to activate nuclear transcription surpasses that of Ace1 and compares favourably with the strong activation domain of the tumor suppressor protein, p53. Our results suggest that 7B2 must possess an activating sequence, a domain which defines all transcriptional activator proteins. Like the acidic activation domains of some transcriptional activators, 7B2 also binds the yeast TATA-box binding protein, an essential polypeptide in the basic transcription machinery. Deletion analysis of the gene encoding 7B2 reveals two independent transcriptional activating sequences in the 185 amino acid protein. It is therefore conceivable that 7B2 not only has a functional role in the secretory pathway but also in the nucleus. Moreover, these findings raise an intriguing question regarding the activation domains of 7B2 and their possible link to 7B2's oncogenic potential.
 ...
PMID:The neuroendocrine protein 7B2 contains unusually potent transcriptional activating sequences. 748 73

The Wilms' tumor suppressor gene WT1 encodes a zinc finger transcription factor, whose expression inhibits the growth of the RM1 Wilms' tumor cell line. Transient transfection of WT1 constructs into 3T3 or 293 cells results in transcriptional repression of a number of cotransfected promoters containing the early growth response gene 1 consensus sequence. We now show that WT1 has properties of a transcriptional activator in RM1 cells, an effect that may be associated with the presence of a mutated p53 gene in these cells. Stable transfection of wild-type WT1 into RM1 cells results in induction of endogenous insulin-like growth factor 2 (IGF2) but not of other previously postulated WT1-target genes. The induction of IGF2 is dramatically enhanced by WT1 mutants encoding an altered transactivation domain. We conclude that IGF2 is a potentially physiological target gene for WT1 and that its induction may contribute to the growth-stimulating effects of WT1 variants.
 ...
PMID:WT1 induces expression of insulin-like growth factor 2 in Wilms' tumor cells. 755 24

Tumor suppressor protein p53 is a potent transcriptional activator and regulates cell growth negatively. To characterize the transcriptional activation domain (TAD) of p53, various point mutants were constructed in the context of Gal4 DNA binding domain and tested for their transactivation ability. Our results demonstrated that the positionally conserved hydrophobic residues shared with herpes simplex virus VP16 and other transactivators are essential for transactivation. Also, the negatively charged residues and proline residues are necessary for full activity, but not essential for the activity of p53 TAD. Deletion analyses showed that p53 TAD can be divided into two subdomains, amino acids 1-40 and 43-73. An in vitro glutathione S-transferase pull-down assay establishes a linear correlation between p53 TAD-mediated transactivation in vivo and the binding activity of p53 TAD to TATA-binding protein (TBP) in vitro. Mutations that diminish the transactivation ability of Gal4-p53 TAD also impair the binding activity to TBP severely. Our results suggest that at least TBP is a direct target for p53 TAD and that the binding strength of TAD to TBP (TFIID) is an important parameter controlling activity of p53 TAD. In addition, circular dichroism spectroscopy has shown that p53 TAD peptide lacks any regular secondary structure in solution and that there is no significant difference between the spectra of the wild type TAD and that of the transactivation deficient mutant type.
 ...
PMID:Transactivation ability of p53 transcriptional activation domain is directly related to the binding affinity to TATA-binding protein. 755 31

p53, the protein encoded by one of the most significant human tumor suppressor genes, is a sequence-specific transcriptional activator. When activated by a double-stranded DNA break, p53 function arrests cells in G1 and can induce apoptosis. Transcriptional activation function is critical for p53 tumor suppression, although transcriptional repressing and nontranscriptional functions of p53 may contribute. p53 activation requires that it bind to TFIID through interactions with TATA box-binding protein (TBP)-associated factors and potentially with TBP. Here, we studied the mechanism of p53 activation using in vitro transcription and a sufficiently high p53 concentration to squelch activated transcription. Squelching is thought to result when target molecules that interact with activation domains are titrated by binding to excess activator. Addition of either excess TFIIB or TFIID but not other proteins required for p53-activated transcription reversed squelching by high p53 concentrations, whereas neither stimulated transcription in reactions without excess p53. These results reveal that both TFIIB and TFIID are inhibited by high concentrations of p53 and suggest that p53 activation may work through direct or indirect interactions with both TFIIB and TFIID.
 ...
PMID:Reversal of in vitro p53 squelching by both TFIIB and TFIID. 756 99


1 2 3 4 5 6 7 8 9 10 Next >>