Disease relevance of GTF3A

• The role of invasion and metastasis-promoting MMPs and their potential regulators, AP-2 and HER2, is currently still unclear in breast cancer [1].
• Loss of AP-2 results in up-regulation of MCAM/MUC18 and an increase in tumor growth and metastasis of human melanoma cells [2].
• HER2-positivity was most often seen in carcinomas having both high nuclear and high cytoplasmic AP-2 expression (P < 0.001) [3].
• Moreover, we demonstrated the interaction between endogenous AP-2 and YY1 factors in the BT-474 mammary adenocarcinoma cell line [4].
• N-ras oncogene-induced transformation of human teratocarcinoma cells PA-1 results in sixfold elevated AP-2 mRNA levels [5].

High impact information on GTF3A

• Acetylation of the N-terminal tails of the core histones directly facilitates the recognition by TFIIIA of the 5S RNA gene within model chromatin templates [6].
• The nucleotide sequence of this conserved DNA on the human Y chromosome suggests that it encodes a protein with multiple "finger" domains, as first described in frog transcription factor IIIA [7].
• The product of the first of these loci (factor A) is present in significant excess in normal fibroblasts, seems to turn over rapidly and may be a dimer or higher polymer [8].
• This effect is specific for 5S RNA genes, since TFIIIA will not form an active template when incubated with a cloned Bombyx mori alanine tRNA gene [9].
• The two 'zinc-finger'-like motifs fold to form a single structural domain and are thus distinct from the independently folded units of the TFIIIA-type zinc fingers [10].

Chemical compound and disease context of GTF3A

• AP-2, a monoclonal antibody (mAb) to alphaIIb beta3, positively stained two human melanoma specimens, indicating expression of this integrin in vivo [11].
• Using modified nuclear lysis and binding conditions, we have examined the binding of an embryonal carcinoma (EC) cell factor, binding factor A, to a stem cell-specific silencer which acts at the DNA level and overlaps the Moloney murine leukemia virus (M-MuLV) proline primer binding site (PBS) [12].
• Anti-clumping factor A immunoglobulin reduces the duration of methicillin-resistant Staphylococcus aureus bacteremia in an experimental model of infective endocarditis [13].
• Expression of the Wilms' tumor gene WT1 in human malignant mesothelioma cell lines and relationship to platelet-derived growth factor A and insulin-like growth factor 2 expression [14].
• The envelope glycoprotein (Env) of HIV-1 interacts with the clathrin-associated adaptor complex AP-2 during the late phase of the viral replication cycle [15].

Biological context of GTF3A

• The human TFIIIA gene (GTF3A) was localized to chromosome band 13q12.3-->q13.1 by fluorescent in situ hybridization (FISH) [16].
• Transcription factor IIIA (TFIIIA) activates 5S ribosomal RNA gene transcription in eukaryotes [17].
• This rat clone was sequenced and the primary structure of the human homolog (termed TFIIIA-intP for TFIIIA-interacting protein) was determined from expressed sequence tags [17].
• In order to identify protein partners for TFIIIA, yeast two-hybrid screens were performed using the C-terminal region of Xenopus TFIIIA as an attractor and a rat cDNA library as a source of potential partners [17].
• It is further demonstrated that this TFIIIA sequence element functions as a protein nuclear export signal in both human cells and frog oocytes [18].

Anatomical context of GTF3A

• The 5S gene-specific transcription factor, TFIIIA, was purified approximately 35,000-fold from HeLa cell extracts using a combination of conventional and affinity chromatographic methods [19].
• This region also contains elements that confer the capacity for activation by AP2, a transcription factor found to be expressed by corneal epithelial cells but not by corneal fibroblasts [20].
• Levels of AP-2 and Sp1 proteins in a panel of melanoma cell lines demonstrated a marked decrease in the ratio of AP-2/Sp1, a decrease that correlated with overexpression of PAR-1 in metastatic melanoma cells [21].
• We have now characterized immunological reagents that enable specific AP-2 family members, including AP-2alpha and AP-2gamma, to be detected in human breast cancer epithelium [22].
• cDNA clones reveal differences between human glial and endothelial cell platelet-derived growth factor A-chains [23].

Associations of GTF3A with chemical compounds

• In fact, AP-2 mRNA is repressed by both TPA and the calcium ionophore A23187 through a delayed response [24].
• For example, after incubation with EDTA at room temperature, the patient's platelets bound little of the monoclonal antibodies AP-2 or T10 (anti-GP IIb-IIIa complex) although normally binding Tab (anti-GP IIb) [25].
• The phenylalanine-based FQQI GLUT4 motif promotes AP-2-dependent internalization less rapidly than a tyrosine-based motif, the classic form of aromatic-based motifs [26].
• A novel jasmonate- and elicitor-responsive element in the periwinkle secondary metabolite biosynthetic gene Str interacts with a jasmonate- and elicitor-inducible AP2-domain transcription factor, ORCA2 [27].
• The remaining GLUT4 is internalized by an AP-2-dependent, nystatin-resistant pathway that requires the FQQI GLUT4 motif [26].

Physical interactions of GTF3A

• In vitro interaction of recombinant human TFIIIA-intP with recombinant Xenopus TFIIIA was demonstrated by immuno-precipitation of the complex using anti-TFIIIA-intP antibody [17].
• These results show that hTFIIIC binds to its promoter sequences in a metal coordinated fashion which differs from that observed for the binding of hTFIIIA to the 5S gene [28].
• Transcription factor IIIC (TFIIIC) is a general RNA polymerase III transcription factor that binds the B-box internal promotor element of tRNA genes and the complex of TFIIIA with a 5S rRNA gene [29].
• P53 physically interacts with mitochondrial transcription factor A and differentially regulates binding to damaged DNA [30].
• NO-treated ECs resulted in a reduction of binding of nuclear proteins to the Egr-1 binding sequences in the platelet-derived growth factor-A promoter region [31].

Regulatory relationships of GTF3A

• NM23-H1 and NM23-H2 repress transcriptional activities of nuclease-hypersensitive elements in the platelet-derived growth factor-A promoter [32].
• In vitro methylation of nuclear respiratory factor-1 binding site suppresses the promoter activity of mitochondrial transcription factor A [33].
• Human platelet-derived growth factor A chain is transcriptionally repressed by the Wilms tumor suppressor WT1 [34].
• FGF-1-induced platelet-derived growth factor-A chain gene expression in endothelial cells involves transcriptional activation by early growth response factor-1 [35].

Other interactions of GTF3A

• In contrast, restoration of 5S RNA gene transcription requires readdition of both TFIIIC and TFIIIA, indicating a promoter-independent interaction between these factors [36].
• Among four distinct components required for accurate transcription in vitro from cloned DNA templates, activities of RNA polymerase III and transcription factor TFIIIA were not significantly affected by virus infection [37].
• Carriage of multiple proinflammatory polymorphisms of IL-1B(o) IL-1 receptor antagonist, tumor necrosis factor A, and IL-10 conferred greater risk, with ORs (and 95% confidence intervals) of 2.8 (1.6-5.1) for one, 5.4 (2.7-10.6) for 2, and 27.3 (7.4-99.8) for 3 or 4 high-risk genotypes [38].
• A role for PDGF-A chain in mediating intimal proliferation has been suggested in human atherosclerosis (Rekhter MD, Gordon D: Does platelet-derived growth factor-A chain stimulate proliferation of arterial mesenchymal cells in human atherosclerotic plaques [39]?
• Regulation of platelet-derived growth factor-A chain by Krüppel-like factor 5: new pathway of cooperative activation with nuclear factor-kappaB [40].

Analytical, diagnostic and therapeutic context of GTF3A

• Interaction of rat TFIIIA with rat TFIIIA-intP was indicated by co-chromatography of the two proteins on DEAE-5PW following fractionation of a rat liver extract on cation, anion and gel filtration resins [17].
• Comparative footprint analyses of hTFIIIA on the human and frog somatic 5 S rRNA gene, measured in titration, competition, and salt-stability experiments, demonstrated a higher affinity of the human factor to the homologous gene [41].
• Transcription factor IIIA (TFIIIA) was purified from cytoplasmic extracts of HeLa cells by developing a simple and efficient procedure employing phosphocellulose under widely differing ionic conditions followed by affinity chromatography on immobilized human 5 S genes [41].
• A monoclonal antibody against human p53 tumor suppressor bound to rat and mouse TFIIIA but not to human TFIIIA in Western blots [42].
• cDNA for rat transcription factor IIIA (TFIIIA) was cloned by degenerate PCR and rapid amplification of cDNA ends [42].

References