We found that knockdown of Daxx in a nontransformed human hepatoc

We found that knockdown of Daxx in a nontransformed human hepatocyte cell line using RNA interference (RNAi) techniques results in significantly increased adenoviral (Ad) replication, including enhanced viral mRNA synthesis AZD9291 molecular weight and viral protein expression. This Daxx restriction imposed upon adenovirus growth is counteracted by early protein E1B-55K (early region 1B 55-kDa protein), a multifunctional regulator

of cell-cycle-independent Ad5 replication. The viral protein binds to Daxx and induces its degradation through a proteasome-dependent pathway. We show that this process is independent of Ad E4orf6 (early region 4 open reading frame 6), known to promote the proteasomal degradation of cellular p53, Mre11, DNA ligase IV, and integrin alpha 3 in combination with E1B-55K. These results illustrate the importance of the PML-NB-associated factor Daxx in virus growth

restriction and suggest that E1B-55K antagonizes innate antiviral activities of Daxx and PML-NBs to stimulate viral replication at a posttranslational level.”
“The alpha-subunit of tetrodotoxin-resistant voltage-gated sodium channel Na(V)1.8 is selectively expressed in sensory neurons. It has been reported that Na(V)1.8 is involved in the transmission of nociceptive information from sensory neurons to the central nervous system in nociceptive [1] and neuropathic [24] pain conditions. Thus Na(V)1.8 has been a promising target to treat chronic pain. Here we discuss the PLK inhibitor recent advances in the study of trafficking mechanism of Na(V)1.8. These pieces of information are particularly important as such trafficking machinery could be new targets for painkillers. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Envelopment of a herpesvirus particle is a complex process

of which much is still to be learned. We previously identified the glycoprotein gpUL132 of human cytomegalovirus (HCMV) as an envelope component of the virion. In its carboxy-terminal portion, gpUL132 contains at least four motifs for sorting of transmembrane proteins to endosomes; among them are one dileucine-based signal and others three tyrosine-based signals of the YXXO and NPXY (where X stands for any amino acid, and O stands for any bulky hydrophobic amino acid) types. To investigate the role of each of these trafficking signals in intracellular localization and viral replication, we constructed a panel of expression plasmids and recombinant viruses in which the signals were rendered nonfunctional by mutagenesis. In transfected cells wild-type gpUL132 was mainly associated with the trans-Golgi network. Consecutive mutation of the trafficking signals resulted in increasing fractions of the protein localized at the cell surface, with gpUL132 mutated in all four trafficking motifs predominantly associated with the plasma membrane.

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