Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.3.2.19 (ubiquitin-protein ligase)
 799 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Herpes simplex virus (HSV) entry into cells is a multistep process that engages the host cell machinery. The proteasome is a large, ATP-dependent, multisubunit protease that plays a critical role in the maintenance of cell homeostasis. A battery of assays were used to demonstrate that proteasome inhibitors blocked an early step in HSV entry that occurred after capsid penetration into the cytosol but prior to capsid arrival at the nuclear periphery. Proteasome-dependent viral entry was not reliant on host or viral protein synthesis. MG132, a peptide aldehyde that competitively inhibits the degradative activity of the proteasome, had a reversible inhibitory effect on HSV entry. HSV can use endocytic or nonendocytic pathways to enter cells. These distinct entry routes were both dependent on proteasome-mediated proteolysis. In addition, HSV successfully entered cells in the absence of a functional host ubiquitin-activating enzyme, suggesting that viral entry is ubiquitin independent. We propose that proteasomal degradation of virion and/or host proteins is required for efficient delivery of incoming HSV capsids to the nucleus.
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PMID:Cellular proteasome activity facilitates herpes simplex virus entry at a postpenetration step. 1823 3

Esophageal achalasia is characterized by abnormal peristalsis of the esophageal body and impaired relaxation of the lower esophageal sphincter (LES); however, its etiology remains unknown. One of the potential causes of esophageal achalasia is herpes simplex virus type 1 (HSV-1). Following infection with HSV-1, a complex interaction between the autoimmune and inflammatory responses is initiated. Viral microRNAs (miRNAs/miRs) serve a crucial role in this interaction. In the present study, the expression of E3 ubiquitin-protein ligase component n-recognition 1 (UBR1) and autophagy-related 16-like 1 (ATG16L1) was assessed in patients with sporadic and classic achalasia as potential targets of the viral miRNAs. We assessed the mRNA levels of target transcripts using reverse transcription-quantitative PCR. UBR1 expression was slightly decreased, although the difference was not significant. However, ATG16L1 expression was significantly decreased in the LES. In conclusion, ATG16L1 expression was reduced in the LES of achalasia patients; therefore, ATG16L1 might be a target of HSV1-miR-H1, and its reduction could be related to the disease mechanism.
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PMID:Autophagy-related 16-like 1 is influenced by human herpes virus 1-encoded microRNAs in biopsy samples from the lower esophageal sphincter muscle during per-oral endoscopic myotomy for esophageal achalasia. 3323 22