Both ERK1 and ERK2 are required for enterovirus 71 (EV71) efficient replication.

Viruses

Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China.

Published: March 2015

It has been demonstrated that MEK1, one of the two MEK isoforms in Raf-MEK-ERK1/2 pathway, is essential for successful EV71 propagation. However, the distinct function of ERK1 and ERK2 isoforms, the downstream kinases of MEKs, remains unclear in EV71 replication. In this study, specific ERK siRNAs and selective inhibitor U0126 were applied. Silencing specific ERK did not significantly impact on the EV71-caused biphasic activation of the other ERK isoform, suggesting the EV71-induced activations of ERK1 and ERK2 were non-discriminative and independent to one another. Knockdown of either ERK1 or ERK2 markedly impaired progeny EV71 propagation (both by more than 90%), progeny viral RNA amplification (either by about 30% to 40%) and protein synthesis (both by around 70%), indicating both ERK1 and ERK2 were critical and not interchangeable to EV71 propagation. Moreover, suppression of EV71 replication by inhibiting both early and late phases of ERK1/2 activation showed no significant difference from that of only blocking the late phase, supporting the late phase activation was more importantly responsible for EV71 life cycle. Taken together, this study for the first time identified both ERK1 and ERK2 were required for EV71 efficient replication and further verified the important role of MEK1-ERK1/2 in EV71 replication.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4379574PMC
http://dx.doi.org/10.3390/v7031344DOI Listing

Publication Analysis

Top Keywords

erk1 erk2
24
ev71 propagation
12
ev71 replication
12
ev71
9
erk2 required
8
ev71 efficient
8
efficient replication
8
specific erk
8
late phase
8
erk1
6

Similar Publications

Aims: This study aimed to delineate the effect of hyperglycemia on the Alu/LINE-1 hypomethylation and in ERK1/2 genes expression in type 2 diabetes with and without cataract.

Methods: This study included 58 diabetic patients without cataracts, 50 diabetic patients with cataracts, and 36 healthy controls. After DNA extraction and bisulfite treatment, LINE-1 and Alu methylation levels were assessed using Real-time MSP.

View Article and Find Full Text PDF

Selumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial.

Nat Med

January 2025

Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

The MEK inhibitor selumetinib induces objective responses and provides clinical benefit in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). To evaluate whether similar outcomes were possible in adult patients, in whom PN growth is generally slower than in pediatric patients, we conducted an open-label phase 2 study of selumetinib in adults with NF1 PNs. The study was designed to evaluate objective response rate (primary objective), tumor volumetric responses, patient-reported outcomes and pharmacodynamic effects in PN biopsies.

View Article and Find Full Text PDF
Article Synopsis
  • Monkeypox (Mpox) is increasingly recognized as a public health issue, and this study uses multi-omics approaches to find therapeutic targets and drug repurposing opportunities to understand its molecular mechanisms.
  • Researchers created a host-pathogen interaction network and identified 55 differentially expressed genes related to Mpox, pinpointing 16 potential drug targets that include both proviral and antiviral genes involved in critical signaling pathways.
  • Promising FDA-approved drug candidates, such as kinase inhibitors and Niclosamide, were identified, aiming to enhance treatment strategies and further the understanding of Mpox's pathology.
View Article and Find Full Text PDF

Transfer RNA-derived fragment production in calves challenged with or co-infected with bovine viral diarrhea virus and in several tissues and blood.

Front Vet Sci

November 2024

Ruminant Diseases and Immunology Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, IA, United States.

Understanding the molecular mechanisms underlying immune response can allow informed decisions in drug or vaccine development, and aid in the identification of biomarkers to predict exposure or evaluate treatment efficacy. The objective of this study was to identify differentially expressed transfer RNA-derived fragments (tRFs) in calves challenged with () or co-infected with and bovine viral diarrhea virus (BVDV). Serum, white blood cells (WBC), liver, mesenteric lymph node (MLN), tracheal-bronchial lymph node (TBLN), spleen, and thymus were collected from Control ( = 2), (MB;  = 3), and co-infected (Dual; = 3) animals, and small RNAs extracted for sequencing.

View Article and Find Full Text PDF
Article Synopsis
  • Multiple myeloma (MM) is a type of blood cancer marked by excessive production of plasma cells that release antibodies, and current research on treatments like Raddeanin A (RA) focuses mainly on solid tumors, leaving a gap in understanding its effects on MM specifically.
  • RA, derived from Anemone raddeana regel, shows promising anti-tumor effects, and this study explores how it may inhibit MM cell growth through network pharmacology and experimental methods, revealing significant interactions with the MAPK signaling pathway.
  • Experimental results demonstrate that RA effectively slows MM cell proliferation, induces apoptosis, alters mitochondrial function, and impacts the expression of key proteins involved in cell growth and survival, suggesting a powerful potential for RA as a treatment for multiple my
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!