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

The yeast GAL4 protein, a transcriptional activator of genes involved in galactose metabolism, binds as a dimer to several closely related seventeen base pair upstream activation sequences (UASGs) that are nearly symmetric about a central dT-dA base pair. A previous study of a GAL4-UASG complex (Carey, M., Kakidani, H., Leatherwood, J., Mostashari, F. and Ptashne, M. (1989) J. Mol. Biol. 209, 423-432) elucidated a pattern of contacts consistent with the protein partially wrapping itself around the helical cylinder, assuming a B-form conformation for the DNA. Alternatively, both monomers could sit on one face of the cylinder if the DNA exists in an underwound conformation such as A-form. Spectroscopic studies that distinguish between these models are reported here. Oligonucleotides containing the consensus UASG or a nine base pair "half site" both exhibit circular dichroism (CD) spectra characteristic of B-form DNA. Two-dimensional NMR studies of the half-site also indicate a B-form conformation. When a GAL4 protein fragment containing the entire DNA-binding and dimerization domains (amino acids 1-140) is bound to the UASG, the CD spectrum above 240 nm changes only slightly, and not in a manner consistent with DNA unwinding. Our studies suggest that the UASG does not adopt an unusual underwound conformation in the absence or presence of the GAL4 protein, and favor the model in which the dimer partially wraps around the helix cylinder.
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PMID:Spectroscopic studies of the DNA binding site of the GAL4 "zinc finger" protein. 201 97

Tissue-restricted POU domain transcription factors, which bind octamer or octamer-like gene sequences, play roles in cellular differentiation and the development of several organs. We have previously identified a POU domain gene, Skn-1a/i, expressed primarily in epidermis, that encodes at least two products through alternative splicing. One of these, Skn-1a, acts as a transcriptional activator, and the other, Skn-1i, contains an inhibitory domain in the NH2 terminus, which prevents DNA-binding in vitro and transcriptional activation in vivo. We now demonstrate that when Skn-1i is expressed in eukaryotic cells it can bind to an octamer site, suggesting that in vivo cellular factors modulate the activity of the inhibitory domain to permit DNA-binding. Yet the inhibitory domain does not allow transactivation by Skn-1i or by a heterologous transactivator containing this domain in cis. Furthermore, we demonstrate that Skn-1a, Tst-1, and Oct-1 are the major octamer-binding proteins in epidermis. Since Skn-1a is primarily expressed in suprabasal cells of the epidermis, we have tested its possible role in the regulation of epidermal papillomaviruses. In transient transfection assays, Skn-1a and Tst-1 can activate the long control region of the epidermis-specific human papillomavirus 1A (HPV-1A). Consistent with these in vivo transcription data, in vitro DNA binding studies identify three octamer-like sites, which are capable of binding Skn-1a, in the HPV-1A long control region. Mutations of all three octamer-like sites prevent transactivation by Skn-1a in transient transfection assays. Taken together, these results provide evidence that Skn-1a and Tst-1 may provide a molecular link between HPV gene expression and epidermal differentiation.
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PMID:Characterization of Skn-1a/i POU domain factors and linkage to papillomavirus gene expression. 918 90

The v-ski oncogene was introduced into mammalian cells in order to study its biochemical and biological properties. v-Ski, produced at relatively high levels by mouse L cells stably transfected with this DNA, was localized to the cell nucleus, was of correct apparent molecular mass, and was capable of complexing with DNA. Transient transfection of reporter plasmids into control or Ski producing mouse L cells revealed that Ski acts as a transcriptional activator of various transcriptional regulatory elements, including CMVie, RSV LTR and SV40. These results indicate that mouse L cells contain the nuclear cofactor(s) required for the ability of v-Ski to bind to DNA and also suggest that the v-Ski present within the cells is functional.
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PMID:Production, characterization and functional activities of v-Ski in cultured cells. 942 40

The proteins SKI and SnoN are implicated in processes as diverse as differentiation, transformation and tumor progression. Until recently, SKI was solely viewed as a nuclear protein with a principal function of inhibiting TGF-beta signaling through its association with the Smad proteins. However, new studies suggest that SKI plays additional roles not only inside but also outside the nucleus. In normal melanocytes and primary non-invasive melanomas, SKI localizes predominantly in the nucleus, whereas in primary invasive melanomas SKI displays both nuclear and cytoplasmic localization. Intriguingly, metastatic melanoma tumors display nuclear and cytoplasmic or predominantly cytoplasmic SKI distribution. Cytoplasmic SKI is functional, as it associates with Smad3 and prevents its nuclear localization mediated by TGF-beta. SKI can also function as a transcriptional activator, targeting the beta -catenin pathway and activating MITF and NrCAM, two proteins involved in survival, migration and invasion. Intriguingly, SKI appears to live a dual life, one as a tumor suppressor and another as a transforming protein. Loss of one copy of mouse ski increases susceptibility to tumorigenesis in mice, whereas its overexpression is associated with cancer progression of human melanoma, esophageal, breast and colon. The molecular reasons for such dramatic change in SKI function appear to result from new acquired activities. In this review, we discuss the mechanisms by which SKI regulates crucial pathways involved in the progression of human malignant melanoma.
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PMID:SKI pathways inducing progression of human melanoma. 1598 36