Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteins that participate in a diverse array of cellular processes can be modified covalently and reversibly on lysine residues by the small ubiquitin-like modifier proteins termed SUMOs. In some instances, such modification profoundly affects protein function, but the biological significance of many SUMOylation events remains unknown. Protein SUMOylation is modulated during many viral infections. Here we demonstrate that the human cytomegalovirus (HCMV) pp71 protein promotes the SUMOylation of its cellular substrate, Daxx. A component of promyelocytic leukemia nuclear bodies, Daxx is a transcriptional corepressor that silences the expression of viral immediate-early (IE) genes at the start of both lytic and quiescent HCMV infections. pp71 is a tegument component delivered directly to cells by infecting HCMV virions. At the start of lytic infections, it travels to the nucleus and stimulates viral IE gene expression by displacing the chromatin remodeling protein ATRX from Daxx and by mediating Daxx degradation through a rare ubiquitin-independent, proteasome-dependent process. Here we report that pp71 also substantially increases the basal level of SUMOylated Daxx observed in cells. To date, consequences of Daxx SUMOylation have not been observed for cellular promoters, and we detected no qualitative change in viral IE gene expression in the absence of pp71-induced Daxx SUMOylation. Thus, while pp71 enhances the basal level of SUMOylated Daxx, the role that this modification plays in regulating Daxx activity in uninfected or HCMV-infected cells remains an enigma.
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PMID:Human cytomegalovirus protein pp71 induces Daxx SUMOylation. 1936 22

The mechanisms of viral persistence of infectious pancreatic necrosis virus (IPNV) are not well understood. In this study we have used a model of IPNV persistently infected CHSE (Chinook salmon embryonic) cells as correlate of persistent infection in fish focusing on differentially expressed genes using subtractive hybridization (SSH). Selected genes were also analyzed by quantitative real-time PCR (qPCR) in persistently infected parr of Atlantic salmon. Persistent infection was established by growing CHSE cells surviving an IPNV infection. Infection in rescued cells was non-lytic with a virus yield of 10(3)-10(5) TCID(50)/ml of supernatant, resembling what can be found during a persistent infection in vivo. By comparing gene expression in persistently infected cell vs. non-infected cells we found an upregulation of genes involved in direct interaction or degradation of viral proteins, proteasome activating subunit 3, and of ATRX (X-linked alpha-thalassemia/mental retardation syndrome), a transcription repressor, which may indicate a repression of viral replication through reduced transcription. Further ephrin B1 (signal-transduction group) was found strongly up-regulated, and receptors for various ephrins are used for cell interaction and as entry points for other viruses in higher vertebrates. Endonuclease/reverse transcriptase 1 (RVT1) was also found highly up-regulated in persistently infected cells. The comparison of persistently infected cells to in vivo infected fish showed that the expression profiles found in CHSE cells give corresponding results for selected genes, as ATRX, ephrin B1 and RVT-1. We observed similar results by use of two independent methods (SSH and qPCR) for 8 out of 15 genes analyzed and the transcript profile of persistently IPNV-infected cells involve upregulation of genes encoding proteins involved in viral protein degradation and translation inhibition. The understanding is that this may contribute to keep the number of virus particles low during viral persistence.
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PMID:Differentially expressed genes following persistent infection with infectious pancreatic necrosis virus in vitro and in vivo. 2015 4