Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20226 (TATA-binding protein)
 1,297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of p185ERBB2 in a total of 34 human gastric carcinoma tissues as well as in corresponding normal mucosa was examined by Western blotting. More than 70% of both tumor tissues and normal mucosa showed p185ERBB2 expression at various levels. Eighteen (55%) cases revealed higher levels of p185ERBB2 in the tumor than in normal mucosa, while 13 (38%) cases showed lower levels in the tumor tissues. Higher expression of p185ERBB2 was frequently observed in well differentiated adenocarcinomas, with the incidence between well differentiated type and poorly differentiated type being significantly different (P less than 0.05). Comparative immunohistochemical analysis revealed the consistent results with p185ERBB2 expression obtained by Western blotting in well differentiated adenocarcinomas. Of the 34 cases, three well differentiated adenocarcinomas had extremely high levels of p185ERBB2. ERBB2 gene was amplified in two of the three tumors, but the amplification differed by the tumor site from where the sample was obtained. Another tumor which showed an extremely high level of p185ERBB2 but no gene amplification demonstrated a high level of binding protein to the TATA box that is located in the promoter of the ERBB2 gene. A high level of TATA-binding protein was also detected in gastric carcinoma cell lines which contain a single copy of ERBB2 gene and a high expression of p185ERBB2.
Cancer Res 1990 Dec 15
PMID:Expression of ERBB2 in human gastric carcinomas: relationship between p185ERBB2 expression and the gene amplification. 197 53

Murine tumor suppressor p53 is phosphorylated in the NH2-terminal transactivating domain at serines 9, 18, and 37. Change of any one of these serines to either alanine or aspartic acid did not alter p53 suppression of transformation of rat embryo fibroblasts by activated ras and E1A. Change of any two of these serines to alanines, however, led to a significant decrease in suppressor function. Substitution of alanines for all three serines caused the most severe loss of suppression and also reduced transactivation functions. The triple substitution had no apparent effects on intracellular accumulation or localization of p53, oligomerization, DNA binding, or interaction with the TFIID TATA-binding protein. In contrast, triple substitution of aspartic acid for serines 9, 18, and 37 had minimal effects on suppression and transactivation by p53. These results argue strongly that phosphorylation of serines 9, 18, and 37 facilitates the suppression and transactivation functions of p53.
Cancer Res 1995 Jun 01
PMID:Serine phosphorylation in the NH2 terminus of p53 facilitates transactivation. 775 94

Human insulin-like growth factor (IGF)-II mRNA has been shown to be expressed at high levels in a variety of tumors, including rhabdomyosarcomas. In addition, many tumors have alterations in p53 expression. To investigate whether p53 regulates IGF-II gene expression, we transfected wild-type p53 expression vectors and luciferase constructs driven by IGF-II P3 promotors into multiple cell lines. We found that p53 reduced, in a dose-dependent manner, both endogenous IGF-II P3 transcripts and transfected P3 luciferase expression. The inhibition of P3 luciferase expression by p53 was more pronounced in the two cell lines that expressed mutant p53 protein, RD, and HTB114. The element responsible for this inhibition was mapped to the minimal promoter region. We also transfected an HPV-16 E6 expression plasmid into CCL13 cells containing functional p53 and found that E6 up-regulated IGF-II P3 activity. Wild-type, but not mutant, p53 interfered with the binding of TATA-binding protein to the TATA motif of P3, although both could directly associate with human TATA-binding protein. Our results suggest that p53 may play a role in regulation of IGF-II gene expression.
Cancer Res 1996 Mar 15
PMID:Regulation of insulin-like growth factor II P3 promotor by p53: a potential mechanism for tumorigenesis. 864 Aug 27

The c-myc promoter has a unique characteristic showing both RNA polymerase II (pol II) and RNA polymerase III (pol III) activities. Previous studies demonstrated that activating PKC results in upregulation of c-myc expression from its pol II promoter. However, how PKC activation affects expression from the pol III promoter of the c-myc gene is not well understood. This study examines the effect of PKC on the pol III transcription from the c-myc gene by using an in vitro system. We report the inhibition of the c-myc pol III transcript by activating PKC. Further, either a phosphocellulose fraction of HeLa whole cell extract (WCE) enriched for transcription factor TF IIIB, or recombinant TATA-box binding protein could restore the inhibited c-myc pol III transcription under conditions that activate PKC. A role has been proposed for the c-myc pol III transcript in the regulation of c-myc gene expression. Therefore, this report discusses the significance of the downregulation of c-myc expression from its pol III promoter and the possible interplay between the pol II and pol III promoters of this gene.
Cancer Lett 1998 Jan 30
PMID:Protein kinase C inhibits transcription from the RNA polymerase III promoter of the human c-myc gene. 948 89

Pax-5 codes for the transcription factor BSAP, which plays an important role in midbrain patterning, B cell development, and lymphoma formation. Pax-5 is known to control gene expression by recognizing its target genes via the NH2-terminal paired domain and by regulating transcription through a COOH-terminal regulatory module consisting of activating and inhibitory sequences. The central region of Pax-5 contains a sequence with significant homology to the first alpha-helix of the paired-type homeodomain. This partial homeodomain has been highly conserved throughout vertebrate evolution because it is found not only in Pax-5 but also in the related Pax-2 and Pax-8 members of the same Pax subfamily. Here we report that the partial homeodomain binds the TATA-binding protein (TBP) and retinoblastoma (Rb) gene product. Both TBP and Rb were shown by coimmunoprecipitation experiments to directly associate with Pax-5 in vivo. The conserved core domain of TBP and the pocket region as well as COOH-terminal sequences of Rb are required for interaction with the partial homeodomain of Pax-5 in in vitro binding assays. Furthermore, Pax-5 was specifically bound only by the underphosphorylated form of Rb. These data indicate that Pax-5 is able to contact the basal transcription machinery through the TBP-containing initiation factor TFIID, and that its activity can be controlled by the cell cycle-regulated association with Rb.
Cancer Res 1999 Apr 01
PMID:The partial homeodomain of the transcription factor Pax-5 (BSAP) is an interaction motif for the retinoblastoma and TATA-binding proteins. 1019 86

Many transcriptional activators are intrinsically unstructured yet display unique, defined conformations when bound to target proteins. Target-induced folding provides a mechanism by which activators could form specific interactions with an array of structurally unrelated target proteins. Evidence for such a binding mechanism has been reported previously in the context of the interaction between the cancer-related c-Myc protein and the TATA-binding protein, which can be modeled as a two-step process in which a rapidly forming, low affinity complex slowly converts to a more stable form, consistent with a coupled binding and folding reaction. To test the generality of the target-induced folding model, we investigated the binding of two widely studied acidic activators, Gal4 and VP16, to a set of target proteins, including TATA-binding protein and the Swi1 and Snf5 subunits of the Swi/Snf chromatin remodeling complex. Using surface plasmon resonance, we show that these activator-target combinations also display bi-phasic kinetics suggesting two distinct steps. A fast initial binding phase that is inhibited by high ionic strength is followed by a slow phase that is favored by increased temperature. In all cases, overall affinity increases with temperature and, in most cases, with increased ionic strength. These results are consistent with a general mechanism for recruitment of transcriptional components to promoters by naturally occurring acidic activators, by which the initial contact is mediated predominantly through electrostatic interactions, whereas subsequent target-induced folding of the activator results in a stable complex.
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PMID:Mechanism of transcription factor recruitment by acidic activators. 1582 52

Previously, we showed that the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist troglitazone at high doses was able to suppress androgen receptor (AR) expression in LNCaP prostate cancer cells independently of PPARgamma. Pharmacologic exploitation of this finding led to STG28, a PPARgamma-inactive analogue of troglitazone with substantially higher potency in AR repression. Considering the pivotal role of AR in prostate tumorigenesis, this study investigates the mechanism by which troglitazone and derivatives suppress AR expression in LNCaP cells. Reverse transcription-PCR and reporter gene assays indicate that this drug-induced AR repression occurs at both mRNA and protein levels. Evidence suggests that troglitazone and derivatives mediate the transcriptional repression of AR by facilitating the ubiquitin-dependent proteasomal degradation of the transcriptional factor Sp1. These agents also cause the proteolysis of two proteins that regulate Sp1-mediated transcription (i.e., the TATA-binding protein-associated factor TAF(II)250 and cyclin D1). However, their involvement in the transcriptional repression of AR is refuted by the finding that small interfering RNA knockdown of these two regulatory proteins does not cause AR down-regulation. STG28 does not cause significant reduction in Sp1 or AR expression in normal prostate epithelial cells. This discriminatory effect underscores the differential susceptibility of malignant versus normal cells to the inhibitory effect of STG28 on cell viability. From a translational perspective, STG28 provides a proof of principle that potent AR-ablative agents could be developed through structural modifications of troglitazone. Moreover, as the control of Sp1 degradation remains unclear, STG28 represents a unique pharmacologic probe to investigate the ubiquitin-proteasome system that regulates Sp1 proteolysis.
Cancer Res 2007 Apr 01
PMID:Peroxisome proliferator-activated receptor gamma-independent suppression of androgen receptor expression by troglitazone mechanism and pharmacologic exploitation. 1740 31

Human extraskeletal myxoid chondrosarcoma (EMC) is caused by a chromosomal translocation that involves TEC (translocated in extraskeletal myxoid chondrosarcoma), and either EWS (Ewing's sarcoma) or hTAF(II)68 (human TATA-binding protein-associated factor II 68), which generates EWS-TEC or hTAF(II)68-TEC fusion proteins, respectively. Although there has been a great deal of progress in characterizing EWS-TEC, there is relatively little known about the biological function of hTAF(II)68-TEC. We have examined the functional consequences of the fusion of the amino terminal domain (NTD) of hTAF(II)68 to TEC in EMC. The chimeric gene encodes a nuclear protein that binds DNA with the same sequence specificity as parental TEC. Nuclear localization of hTAF(II)68-TEC was dependent on the DNA binding domain, and we identified a cluster of basic amino acids in the DNA binding domain, KRRR, that specifically mediate the nuclear localization of hTAF(II)68-TEC. The transactivation activity of hTAF(II)68-TEC was higher than TEC towards a known target promoter that contained several TEC binding sites. Finally, deletion analysis of hTAF(II)68-TEC indicated that the hTAF(II)68 NTD, and the AF1 and AF2 domains of hTAF(II)68-TEC are necessary for full transactivation potential. These results suggest that the oncogenic effect of the t(9;17) translocation may be due to the hTAF(II)68-TEC chimeric protein and that fusion of the hTAF(II)68 NTD to the TEC protein produces a gain of function chimeric product.
Int J Cancer 2008 Jun 01
PMID:The hTAF II 68-TEC fusion protein functions as a strong transcriptional activator. 1833 Sep 2

RNA transcription by all the three RNA polymerases (RNAPs) is tightly controlled, and loss of regulation can lead to, for example, cellular transformation and cancer. While most transcription factors act specifically with one polymerase, a small number have been shown to affect more than one polymerase to coordinate overall levels of transcription in cells. Here we show that TLS (translocated in liposarcoma), a protein originally identified as the product of a chromosomal translocation and which associates with both RNAP II and the spliceosome, also represses transcription by RNAP III. TLS was found to repress transcription from all three classes of RNAP III promoters in vitro and to associate with RNAP III genes in vivo, perhaps via a direct interaction with the pan-specific transcription factor TATA-binding protein (TBP). Depletion of TLS by small interfering RNA (siRNA) in HeLa cells resulted in increased steady-state levels of RNAP III transcripts as well as increased RNAP III and TBP occupancy at RNAP III-transcribed genes. Conversely, overexpression of TLS decreased accumulation of RNAP III transcripts. These unexpected findings indicate that TLS regulates both RNAPs II and III and supports the possibility that cross-regulation between RNA polymerases is important in maintaining normal cell growth.
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PMID:TLS inhibits RNA polymerase III transcription. 1984 Oct 68

Accumulating evidence indicates that TBP (TATA-binding protein)-like protein (TLP) contributes to the regulation of stress-mediated cell cycle checkpoint and apoptotic pathways, although its physiological target genes have remained elusive. In the present study, we have demonstrated that human TAp63 is one of the direct transcriptional target genes of TLP. Enforced expression of TLP results in the transcriptional induction of the endogenous TAp63, but not of the other p53 family members such as TAp73 and p53. Consistent with these results, small interference RNA-mediated knockdown led to a significant down-regulation of the endogenous TAp63. Luciferase reporter assay and chromatin immunoprecipitation analysis revealed that the genomic region located at positions -487 to -29, where +1 represents the transcriptional initiation site of TAp63, is required for TLP-dependent transcriptional activation of TAp63 and also TLP is efficiently recruited onto this region. Additionally, cells treated with anti-cancer drug etoposide underwent apoptosis in association with the transcriptional enhancement of TAp63 in a p53-independent manner, and the knockdown of the endogenous TLP reduced etoposide-induced apoptosis through repression of TAp63 expression. Taken together, our present study identifies a TLP-TAp63 pathway that is further implicated in stress-induced apoptosis.
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PMID:TATA-binding Protein (TBP)-like Protein Is Engaged in Etoposide-induced Apoptosis through Transcriptional Activation of Human TAp63 Gene. 1985 4


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