Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of different picornavirus internal ribosome entry site (IRES) elements to direct initiation of protein synthesis has been assayed in different cell lines in the presence and absence of viral proteases that inhibit cap-dependent protein synthesis. Reporter plasmids that express dicistronic mRNAs, containing different IRES elements, with the general structure CAT/IRES/LUC, have been assayed. In each plasmid, the CAT sequence encodes chloramphenicol acetyl transferase and the LUC sequence encodes luciferase. The poliovirus (PV) 2A protease and the foot-and-mouth disease virus (FMDV) Lb protease induce the cleavage of the translation initiation factor elF4G and hence inhibit the activity of the cap-binding complex, elF4F. In human osteosarcoma (HTK-143) cells, each of the various IRES elements functioned efficiently. In these cells, the co-expression of the viral proteases severely inhibited the expression of CAT, but the proteases had little effect on the activities of the various IRES elements. In contrast, in baby hamster kidney (BHK) cells, the efficiencies of the different IRES elements varied significantly, whereas, in normal rat kidney (NRK) cells, each of the IRES elements was relatively inefficient. In both BHK and NRK cells, the activities of those IRES elements that functioned inefficiently were strongly stimulated by the co-expression of the PV 2A or FMDV Lb proteases. This stimulation was independent of the loss of cap-dependent protein synthesis and was not achieved by the co-expression of the C-terminal fragment of elF4G. The results suggest that the PV 2A and FMDV Lb proteases induce the cleavage of another cellular protein, in addition to elF4G, which influences IRES function.
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PMID:Recognition of picornavirus internal ribosome entry sites within cells; influence of cellular and viral proteins. 958 94

Coxsackievirus B3 (CVB3), an important human causative pathogen for viral myocarditis, pancreatitis, and meningitis, has evolved different strategies to manipulate the host signaling machinery to ensure successful viral infection. We previously revealed a crucial role for the ERK1/2 signaling pathway in regulating viral infectivity. However, the detail mechanism remains largely unknown. Grb2-associated binder 1 (GAB1) is an important docking protein responsible for intracellular signaling assembly and transduction. In this study, we demonstrated that GAB1 was proteolytically cleaved after CVB3 infection at G175 and G436 by virus-encoded protease 2A(pro), independent of caspase activation. Knockdown of GAB1 resulted in a significant reduction of viral protein expression and virus titers. Moreover, we showed that virus-induced cleavage of GAB1 is beneficial to viral growth as the N-terminal proteolytic product of GAB1 (GAB1-N1-174) further enhances ERK1/2 activation and promotes viral replication. Our results collectively suggest that CVB3 targets host GAB1 to generate a GAB1-N1-174 fragment that enhances viral infectivity, at least in part, via activation of the ERK pathway. The findings in this study suggest a novel mechanism that CVB3 employs to subvert the host signaling and facilitate consequent viral replication.
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PMID:Enhanced enteroviral infectivity via viral protease-mediated cleavage of Grb2-associated binder 1. 2618 72

In a previous study the ERK1/2 pathway was found to be crucially involved in positive regulation of the enterovirus A 71(EV-A71) IRES (vIRES), thereby contributing to the efficient replication of an important human enterovirus causing death in young children (<5yrs) worldwide. This study focuses on unraveling more about the detailed mechanism of ERK's involvement in this regulation of vIRES. Through the use of siRNAs and specifically pharmacological inhibitor U0126, the ERK cascade was shown to positively regulate EV-A71-mediated cleavage of eIF4GI that established the cellular conditions which favour vIRES-dependent translation. Site-directed mutagenesis of the viral 2A protease (2Apro) was undertaken to show that the positive regulation of virus replication by the ERK cascade was mediated through effects on both the cis-cleavage of the viral polyprotein by 2Apro and its trans-cleavage of cellular eIF4GI. This ERK-2Apro linked network coordinating vIRES efficiency was also found in other important human enteroviruses. This identification of the ERK cascade as having a key role in maintaining the 2Apro proteolytic activity required to maximize enterovirus IRES activity, expands current understanding of the diverse functions of the ERK signaling cascade in the regulation of viral translation, therefore providing a potentially comprehensive drug target for anti-enterovirus infection.
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PMID:Regulation of enterovirus 2A protease-associated viral IRES activities by the cell's ERK signaling cascade: Implicating ERK as an efficiently antiviral target. 2835 8