Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenovirus E1B 55,000-molecular-weight protein (55K) binds to host cell p53, stabilizing it, greatly increasing its affinity for its cognate DNA-binding site, and converting it from a regulated activator to a constitutive repressor. Here we analyzed the mechanism of repression by the p53-E1B 55K complex. E1B 55K repression requires that 55K be tethered to the promoter by binding directly to DNA-bound p53. Transcription from an assembled, p53-activated preinitiation complex was not repressed by the subsequent addition of E1B 55K, suggesting that either sites of 55K interaction with p53 or targets of 55K in the preinitiation complex are blocked. Specific E1B 55K repression was observed in reactions lacking TFIIA and with recombinant TATA-binding protein in place of TFIID, conditions under which p53 does not activate transcription. Thus, E1B 55K does not simply inhibit a p53-specific activation mechanism but rather blocks basal transcription. As a consequence, E1B 55K may repress transcription from any promoter with an associated p53-binding site, no matter what other activators associate with the promoter. E1B 55K did not repress basal transcription in reactions with recombinant and highly purified general transcription factors and RNA polymerase II but rather required a corepressor that copurifies with the polymerase.
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PMID:Corepressor required for adenovirus E1B 55,000-molecular-weight protein repression of basal transcription. 1020 64

Adenovirus large E1A, Epstein-Barr virus Zebra, and herpes simplex virus VP16 were studied as models of animal cell transcriptional activators. Large E1A can activate transcription from a TATA box, a result that leads us to suggest that it interacts with a general transcription factor. Initial studies showed that large E1A binds directly to the TBP subunit of TFIID. However, analysis of multiple E1A and TBP mutants failed to support the significance of this in vitro interaction for the mechanism of activation. Recent studies to be reported elsewhere indicate that conserved region 3 of large E1A, which is required for its activation function, binds to one subunit of a multisubunit protein that stimulates in vitro transcription in response to large E1A and other activators. A method was developed for the rapid purification of TFIID approximately 25,000-fold to near homogeneity from a cell line engineered to express an epitope-tagged form of TBP. Purified TFIID contains 11 major TAFs ranging in mass from approximately 250 to 20 kD. Zta and VP16, but not large E1A, greatly stimulate the rate and extent of assembly of a TFIID-TFIIA complex on promoter DNA (DA complex). For VP16, this is a function of the carboxy-terminal activation subdomain. An excellent correlation was found between the ability of VP16C mutants to stimulate DA complex assembly and their ability to activate transcription in vivo. Consequently, for a subset of activation domains, DA complex assembly activity is an important component of the overall mechanism of activation.
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PMID:Mechanisms of viral activators. 1038 88

The assembly and stability of the RNA polymerase II transcription preinitiation complex on a eukaryotic core promoter involves the effects of TFIIA on the interaction between TATA-binding protein (TBP) and DNA. To extend our understanding of these interactions, we characterized properties of ALF, a germ cell-specific TFIIA-like factor. ALF was able to stabilize the binding of TBP to DNA, but it could not stabilize TBP mutants A184E, N189E, E191R, and R205E nor could it facilitate binding of the TBP-like factor TRF2/TLF to a consensus TATA element. However, phosphorylation of ALF with casein kinase II resulted in the partial restoration of complex formation using mutant TBPs. Studies of ALF-TBP complexes formed on the Adenovirus Major Late (AdML) promoter revealed protection of the TATA box and upstream sequences from -38 to -20 (top strand) and -40 to -22 (bottom strand). The half-life and apparent K(D) of this complex was determined to be 650 min and 4.8 +/- 2.7 nm, respectively. The presence of ALF or TFIIA did not significantly alter the ability of TBP to bind TATA elements from several testis-specific genes. Finally, analysis of the distinct, nonhomologous internal regions of ALF and TFIIAalpha/beta using circular dichroism spectroscopy provided the first evidence to suggest that these domains are unordered, a result consistent with other genetic and biochemical properties. Overall, the results show that while the sequence and regulation of the ALF gene are distinct from its somatic cell counterpart TFIIAalpha/beta, the TFIIAgamma-dependent interactions of these factors with TBP are nearly indistinguishable in vitro. Thus, a role for ALF in the assembly and stabilization of initiation complexes in germ cells is likely to be similar or identical to the role of TFIIA in somatic cells.
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PMID:The germ cell-specific transcription factor ALF. Structural properties and stabilization of the TATA-binding protein (TBP)-DNA complex. 1210 78