Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transcriptional programme of the herpes viruses is organised into three principal phases. The immediate-early (IE) genes are the first to be transcribed, by the pre-existing host RNA polymerase II, and their promoters are strongly stimulated by a polypeptide component of the virus particle. The E and L gene promoters become active only after the appearance of IE gene products. Genetic and biochemical evidence has shown that the HSV-1 IE polypeptide Vmw175 (ICP 4) is essential for the trans activation of HSV early promoters, but the role of none of the other four IE gene products was known. This paper describes functional tests that show, by co-transfection of recombinant plasmids into HeLa cells, that (i) Vmw175 alone can activate an HSV-1 E gene promoter, (ii) the four other HSV-1 IE gene products by themselves are unable to activate transcription, (iii) the combination of Vmw175 plus the product of IE gene 1, Vmw110 (ICP 0), is a much better activator than Vmw175 alone, (iv) cloned IE gene products of human cytomegalovirus (CMV), varicella-zoseter virus (VZV) and pseudorabies virus (PRV) can also activate transcription from an HSV-1 early promoter, and (v) this activation also occurs with cellular promoters.
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PMID:Trans activation of transcription by herpes virus products: requirement for two HSV-1 immediate-early polypeptides for maximum activity. 609 66

ICP4 of herpes simplex virus is responsible for the activation of viral transcription during infection. It also efficiently activates and represses transcription in vitro depending on the promoter context. The contacts made between ICP4 and the cellular proteins that result in activated transcription have not been identified. The inability of ICP4 to activate transcription with TATA-binding protein in place of TFIID and the requirement for an initiator element for efficient ICP-4-activated transcription suggest that coactivators, such as TBP-associated factors, are involved (B. Gu and N. DeLuca, J. Virol. 68:7953-7965, 1994). In this study we showed that ICP4 activates transcription in vitro using an immunopurified TFIID, indicating that TBP-associated factors may be a sufficient subset of coactivators for ICP4-activated transcription. Similar to results seen in vivo, the presence of the ICP4 C-terminal region (amino acids 774 to 1298) was important for activation in vitro. With epitope-tagged ICP4 molecules in immunoaffinity experiments, it was shown that the C-terminal region was also required for ICP4 to interact with TFIID present in a crude transcription factor fraction. In the same assay, ICP4 was unable to interact with the basal transcription factors, TFIIB, TFIIE, TFIIF, and TFIIH and RNA polymerase II. ICP4 could also interact with TBP, independent of the C-terminal region. However, reflective of the interaction between ICP4 and TFIID, the ICP4 C-terminal region was required for an interaction with FAF250-TBP complexes and with TAF250 alone. Therefore, the interfaces or conformation of TBP mediating the interaction between ICP4 and TBP in solution is probably masked when TBP is bound to TAF250. With a series of mutant ICP4 molecules purified from herpes simplex virus-infected cells, it was shown that ICP4 molecules that can bind DNA and interact with TAF250 could activate transcription. Taken together, these results demonstrate that ICP4 interaction with TFIID involves the TAF250 molecule and the C-terminal region of ICP4 and that this interaction is part of the mechanism by which ICP4 activates transcription.
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PMID:Interaction of the viral activator protein ICP4 with TFIID through TAF250. 864 20

The eukaryotic transcription elongation factor 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB) sensitivity inducing factor (DSIF), is involved in regulating the processivity of RNA polymerase II. DSIF plays also a role in transcriptional activation, and in concert with the negative elongation factor NELF causes promoter proximal pausing of RNA polymerase II. Furthermore, DSIF has also been implicated in regulating the transcription of the human immunodeficiency virus proviral DNA. Human DSIF is composed of the two subunits, hSpt4 (p14) and hSpt5 (p160), corresponding to the yeast homologs Spt4 and Spt5. Here we show the purification and characterization of the small subunit, hSpt4. We were able to purify the protein in a soluble form separately from the larger hSpt5 subunit. CD and NMR spectroscopy show that the purified protein hSpt4 exhibits an alpha/beta topology with a well defined tertiary structure. Furthermore metal analysis by ICP-OES indicates that the protein contains a functional 4-Cys Zn-finger.
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PMID:The small hSpt4 subunit of the human transcription elongation factor DSIF is a Zn-finger protein with alpha/beta type topology. 1837 78