Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.25.1 (proteasome)
28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A rabbit antiserum prepared against disrupted sucrose-banded HIV-1 virus (strain FRE-3) reacted with antigens present in nuclear inclusions, pathognomonic for human cytomegalovirus (HCMV). This cross-reactivity was observed in autopsy specimens from individuals infected with CMV, in the presence or absence of co-infection with HIV-1. A Towbin immunoassay showed that the serum reacted specifically with the HCMV major capsid protein (MCP, 153 kDa), both in the nuclear fraction of infected cells and in virions. Direct evidence that these proteins share antigenic determinants was provided by the two-way cross-reactivity of affinity-selected antibodies (i.e., anti-MCP with HIV-1 gag precursor Pr55; anti-Pr55 with MCP). All four strains of HCMV tested showed this reactivity, but the counterpart proteins of simian CMV and herpes simplex virus type 1 did not, indicating that the determinant is not common to all herpes group viruses.
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PMID:Evidence that HIV-1 gag precursor shares antigenic sites with the major capsid protein of human cytomegalovirus. 169 65

The gene encoding the 142-kDa major capsid protein (MCP142) of pseudorabies virus (PrV) was isolated and sequenced. Nucleotide sequence analysis revealed that the MCP142 gene has a single open reading frame of 3993 nucleotides (nt) encoding 1330 amino acids. The 4400-nt major RNA from the MCP142 gene was detected in PrV-infected cells. The 5' end of the transcript was located 60 nt upstream of the initiation codon. The 3' end of the transcript was located 18 nt downstream of a putative poly(A) signal sequence TATAAA and 133 nt downstream of the termination codon. In comparing amino acid sequence homology between MCP142 of PrV and other available herpesviruses MCP was shown to have 58% homology with herpes simplex virus type 1 and varicella-zoster virus, 27% with Epstein-Barr virus, and 24% with human herpesvirus 6 and human cytomegalovirus. It has greater homology with those of the alpha-herpesviruses than with those of the beta-herpesviruses and the gamma-herpesviruses.
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PMID:Nucleotide sequence and transcriptional mapping of the major capsid protein gene of pseudorabies virus. 171 89

Systematic solid-phase synthesis of all possible overlapping nonapeptides of the 1381 amino acid sequence of the Epstein-Barr virus major capsid protein (EBV-MCP) was used to identify the position of linear antigen epitopes on this protein as recognised by human polyclonal antisera. Antisera were selected for reactivity with EBV-MCP on immunoblots. The results show that antibodies from different individual donors may recognise EBV-MCP through binding to a variety of different epitopes. These epitopes are localized at random over the protein backbone though some non-binding areas are also present. In addition, ten 'hot-spots' were identified containing closely-spaced reactive peptides (epitope-clusters) recognised by most (greater than or equal to 70%) individuals. No significant correlation was found between the actual location of these epitope-clusters and computer predictions using either hydrophilicity plots, secondary structure plots or a combination of (additional) parameters. Epitope-clusters generally were located in regions of indifferent or hydrophilic nature and mostly contained predicted beta-turn configurations. Only one epitope-cluster was located within a region of sequence homology with the MCPs of herpes simplex virus type 1 and varicella-zoster virus. The present study demonstrates the potential of using systematic peptide synthesis to define serologically relevant linear epitopes on large and relatively unexplored viral polypeptides.
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PMID:Epitope-mapping on the Epstein-Barr virus major capsid protein using systematic synthesis of overlapping oligopeptides. 246 Apr 80

Transcriptional stimulation by the model activator GAL4-VP16 (a chimeric protein consisting of the DNA-binding domain of the yeast activator GAL4 and the acidic activation domain of the herpes simplex virus protein VP16) involves a series of poorly understood protein-protein interactions between the VP16 activation domain and components of the RNA polymerase II general transcription machinery. One of these interactions is the VP16-mediated binding and recruitment of transcription factor TFIIB. However, TATA box-binding protein (TBP)-associated factors (TAFs), or coactivators, are required for this interaction to culminate in productive transcription complex assembly, and one such TAF, Drosophila TAF40, reportedly forms a ternary complex with VP16 and TFIIB. Due to TFIIB's central role in gene activation, we sought to directly visualize the surfaces of this protein that mediate formation of the ternary complex. We developed an approach called protease footprinting in which the broad-specificity proteases chymotrypsin and alkaline protease were used to probe binding of 32P-end-labeled TFIIB to GAL4-VP16 or TAF40. Analysis of the cleavage products revealed two regions of TFIIB protected by VP16 from protease attack, one of which overlapped with a region protected by TAF40. The close proximity of the VP16 and TAF40 binding sites on the surface of TFIIB suggests that this region could act as a regulatory interface mediating the effects of activators and coactivators on transcription complex assembly.
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PMID:Protease footprinting reveals a surface on transcription factor TFIIB that serves as an interface for activators and coactivators. 759 78

This paper reports the first spontaneous isolation of two DNA duplication variants in the unique long (UL) component of herpes simplex virus type 1 (HSV-1) strain 17+ genome, one (1719) with a duplication of 7.5 kb DNA sequences centered around OriL and the other (1740In) with a 356 bp DNA duplication between the UL19 (MCP) and UL20 open reading frames (ORFs). The variant 1719 is stable with the rare isolation of a wild type (strain 17+) genome presumably generated by the excision of the duplicated sequences during homologous recombination. Because of the 7.5 kb duplication, UL29 (DBP) is diploid and UL30 (DNA pol) is present as one complete and one partial copy. Although duplication in the variant 1740In involved sequences from the UL20 ORF, the virus produces an intact UL20 gene product. Both variants show normal growth characteristics when compared with the parental viruses. DNA duplications in these variants suggest a link between replication and recombination in HSV-1.
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PMID:Isolation and characterization of two herpes simplex virus type 1 variants containing duplication of sequences within the unique long component of their genomes. 767 39

We have used the yeast GAL4 two-hybrid system to examine interactions between the human cytomegalovirus (HCMV) major capsid protein (MCP, encoded by UL86) and the precursor assembly protein (pAP, encoded by UL80.5 and cleaved at its carboxyl end to yield AP) and found that (i) the pAP interacts with the MCP through residues located within the carboxy-terminal 21 amino acids of the pAP, called the carboxyl conserved domain (CCD); (ii) the pAP interacts with itself through a separate region, called the amino conserved domain (ACD), located between amino acids His34 and Arg52 near the amino end of the molecule; (iii) the simian CMV (SCMV) pAP and AP can interact with or replace their HCMV counterparts in these interactions, whereas the herpes simplex virus pAP and AP homologs cannot; and (iv) the HCMV and SCMV maturational proteinase precursors (ACpra, encoded by UL80a and APNG1, respectively) can interact with the pAP and MCP. The ACD and CCD amino acid sequences are highly conserved among members of the betaherpesvirus group and appear to have counterparts in the alpha- and gammaherpesvirus pAP homologs. Deleting the ACD from the HCMV pAP, or substituting Ala for a conserved Leu in the ACD, eliminated detectable pAP self-interaction and also substantially reduced MCP binding in the two-hybrid assay. This finding indicates that the pAP self-interaction influences the pAP-MCP interaction. Immunofluorescence studies corroborated the pAP-MCP interaction detected in the GAL4 two-hybrid experiments and showed that nuclear transport of the MCP was mediated by pAP but not AP. We conclude that the pAP interacts with the MCP, that this interaction is mediated by the CCD and is influenced by pAP self-interaction, and that one function of the pAP-MCP interaction may be to provide a controlled mechanism for transporting the MCP into the nucleus.
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PMID:Human cytomegalovirus capsid assembly protein precursor (pUL80.5) interacts with itself and with the major capsid protein (pUL86) through two different domains. 898 37

N-acetyl-L-leucyl-L-leucyl-L-norleucinal (LLnL), which reversibly inhibits the proteasome in addition to other proteases, and a more specific irreversible inhibitor of the proteasome, lactacystin, were found to cause the accumulation of major histocompatibility complex (MHC) class I heavy chains in the cytosol of the beta2-microglobulin-deficient cell line Daudi and the TAP-deficient cell line .174. These cell lines, which are severely impaired in their ability to fold MHC class I heavy chain, showed an accumulation of soluble class I heavy chains at different rates over a period of hours in the presence of LLnL. The accumulation of soluble class I heavy chains in the presence of either LLnL or lactacystin was easily revealed in Daudi and .174 but almost undetectable in a Daudi transfectant expressing beta2-microglobulin and in 45.1, the wild-type parent of .174. The soluble class I heavy chain was also found to be devoid of its N-linked glycan and to be located in the cytosol. When the gene for ICP47, a herpes simplex virus protein that blocks the translocation of peptides into the endoplasmic reticulum, was transfected into 45.1, a similar accumulation of soluble MHC class I heavy chain was detectable. These data suggest that in cells where the MHC class I molecule is unable to assemble properly, the misfolded heavy chain is removed from the endoplasmic reticulum to the cytosol, deglycosylated, and degraded by the proteasome.
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PMID:Misfolded major histocompatibility complex class I heavy chains are translocated into the cytoplasm and degraded by the proteasome. 905 Aug 76

Herpes simplex virus type 1 (HSV-1) infection causes the active degradation of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), and this process is reliant on the expression of the HSV-1 immediate-early protein Vmw110. In this study we investigated in more detail the mechanism by which the degradation occurs, the domains of Vmw110 which are required, and whether Vmw110 is by itself sufficient for the effect. We found that proteasome inhibitors prevented the degradation of DNA-PKcs, indicating the involvement of a proteasome pathway. Furthermore, the continued activity of DNA-PK during infection in the presence of these inhibitors indicated that Vmw110 does not directly alter the enzyme activity of DNA-PKcs prior to its degradation in a normal infection. Indeed, Vmw110 was found to bind to neither the catalytic nor Ku subunits of DNA-PK. Using mutant Vmw110 viruses we show that the RING finger domain of Vmw110 is essential for the induced degradation of DNA-PKcs but that the ability of Vmw110 to bind to a cellular ubiquitin-specific protease (HAUSP) is not required. When expressed in the absence of other viral proteins, Vmw110 was sufficient to cause the degradation of DNA-PKcs, indicating that the effect on the stability of DNA-PKcs was a direct consequence of Vmw110 activity and not an indirect Vmw110-dependent effect of virus infection. Finally, the Vmw110-induced degradation of DNA-PKcs and loss in DNA-PK activity appears to be beneficial to HSV-1 infection, as virus replication was more efficient in cells lacking DNA-PKcs, especially at low multiplicities of infection.
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PMID:Herpes simplex virus type 1 immediate-early protein vmw110 induces the proteasome-dependent degradation of the catalytic subunit of DNA-dependent protein kinase. 984 70

The ability of herpes simplex virus type 1 (HSV-1) to attain a latent state in sensory neurones and reactivate periodically is crucial for its biological and clinical properties. The active transcription of the entire 152 kb viral genome during lytic replication contrasts with the latent state, which is characterized by the production of a single set of nuclear-retained transcripts. Reactivation of latent genomes to re-initiate the lytic cycle therefore involves a profound change in viral transcriptional activity, but the mechanisms by which this fundamentally important process occurs are yet to be well understood. In this report we show that the stimulation of the onset of viral lytic infection mediated by the viral immediate-early (IE) protein Vmw110 is strikingly inhibited by inactivation of the ubiquitin-proteasome pathway. Similarly, the Vmw110-dependent reactivation of quiescent viral genomes in cultured cells is also dependent on proteasome activity. These results constitute the first demonstration that the transcriptional activity of a viral genome can be regulated by protein stability control pathways.
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PMID:A viral activator of gene expression functions via the ubiquitin-proteasome pathway. 985 73

Examination of cells at the early stages of herpes simplex virus type 1 infection revealed that the viral immediate-early protein Vmw110 (also known as ICP0) formed discrete punctate accumulations associated with centromeres in both mitotic and interphase cells. The RING finger domain of Vmw110 (but not the C-terminal region) was essential for its localization at centromeres, thus distinguishing the Vmw110 sequences required for centromere association from those required for its localization at other discrete nuclear structures known as ND10, promyelocytic leukaemia (PML) bodies or PODs. We have shown recently that Vmw110 can induce the proteasome-dependent loss of several cellular proteins, including a number of probable SUMO-1-conjugated isoforms of PML, and this results in the disruption of ND10. In this study, we found some striking similarities between the interactions of Vmw110 with ND10 and centromeres. Specifically, centromeric protein CENP-C was lost from centromeres during virus infection in a Vmw110- and proteasome-dependent manner, causing substantial ultrastructural changes in the kinetochore. In consequence, dividing cells either became stalled in mitosis or underwent an unusual cytokinesis resulting in daughter cells with many micronuclei. These results emphasize the importance of CENP-C for mitotic progression and suggest that Vmw110 may be interfering with biochemical mechanisms which are relevant to both centromeres and ND10.
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PMID:Specific destruction of kinetochore protein CENP-C and disruption of cell division by herpes simplex virus immediate-early protein Vmw110. 1007 24


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