Analysis of MHC Class I Processing Pathways That Generate a Response to Vaccinia Virus Late Proteins.

Use of recombinant viral vectors encoding nonnative Ags is an attractive mechanism for the generation of protective Ab, CD4 T cell (T), and CD8 T cell (T) responses in vivo following immunization. However, the life cycle and tropism of the viral vector, and its interactions with various components of the immune system, must be fully understood to maximize the efficacy of any vaccination strategies. Ab and T responses typically target native Ags driven by late promoters in vaccinia virus (VACV)-based vectors.

Interaction of Beclin 1 with survivin regulates sensitivity of human glioma cells to TRAIL-induced apoptosis.

We reported a novel interaction between Beclin 1, a key regulator of autophagy, and survivin, a member of the inhibitor of apoptosis protein family. We found that knock-down of Beclin 1 down-regulated survivin protein, and the turnover rate of survivin was increased when Beclin 1 expression was silenced. Knock-down of Beclin 1 sensitized glioma cells to TRAIL-induced apoptosis, and introduction of survivin antagonized the sensitizing effect, suggesting that down-regulation of survivin mediates the enhanced sensitivity to TRAIL-induced apoptosis.

Potentiation of the growth inhibition activity of 2-({4-[4-(acridin-9-ylamino)phenylthio]phenyl}(2-hydroxyethyl)amino)ethan-1-ol (CK0402) by Herceptin in SKBR-3 human breast cancer cells.

The 9-aminoacridine derivative, 2-({4-[4-(acridin-9-ylamino)phenylthio]phenyl}(2-hydroxyethyl) amino)ethan-1-ol (CK0402) was selected as a potential anticancer agent among a series of sulfur-containing 9-aminoacridine analogues. CK0402 is a topoisomerase II inhibitor and has been shown to exert impressive anticancer activities in both in vitro and in vivo assays. In the present study, we tested the effects of CK0402 in a panel of established human breast cancer cells with varying ER and HER2/neu status.

Silencing of elongation factor-2 kinase potentiates the effect of 2-deoxy-D-glucose against human glioma cells through blunting of autophagy.

2-Deoxy-d-glucose (2-DG), a synthetic glucose analogue that acts as a glycolytic inhibitor, is currently being evaluated in the clinic as an anticancer agent. In this study, we observed that treatment of human glioma cells with 2-DG activated autophagy, a highly conserved cellular response to metabolic stress and a catabolic process of self-digestion of intracellular organelles for energy use and survival in stressed cells. The induction of autophagy by 2-DG was associated with activation of elongation factor-2 kinase (eEF-2 kinase), a structurally and functionally unique enzyme that phosphorylates eEF-2, leading to loss of affinity of this elongation factor for the ribosome and to termination of protein elongation.

A viral protein that blocks Arf1-mediated COP-I assembly by inhibiting the guanine nucleotide exchange factor GBF1.

Many viruses modify cellular processes for their own benefit. The enterovirus 3A protein inhibits endoplasmic reticulum (ER)-to-Golgi transport, a function previously suggested to be important for viral suppression of immune responses. Here, we show that a virus carrying a 3A protein defective in inhibiting ER-to-Golgi transport is indeed less virulent in mice, and we unravel the mechanism by which 3A inhibits this trafficking step.

Dynamics of GBF1, a Brefeldin A-sensitive Arf1 exchange factor at the Golgi.

Trafficking through the Golgi apparatus requires members of the Arf family of GTPases, whose activation is regulated by guanine nucleotide exchange factors (GEFs). Once activated, Arf-GTP recruits effectors such as coat complexes and lipid-modifying enzymes to specific membrane sites, creating a domain competent for cargo concentration and transport. GBF1 is a peripherally associated Arf GEF involved in both endoplasmic reticulum-Golgi and intra-Golgi transport.