Ricin toxin, an A-B toxin from Ricinus communis, induces cell death through the inhibition of protein synthesis. The toxin binds to the cell surface via its B chain (RTB) followed by its retrograde trafficking through intracellular compartments to the ER where the A chain (RTA) is transported across the membrane and into the cytosol. Ricin A chain is transported across the ER membrane utilizing...

Semi-synthetic triterpenoids are antioxidant inflammation modulator (AIM) compounds that inhibit tumor cell growth and metastasis. Compounds in the AIM class bind to Keap1 and attenuate Nrf2 degradation. In the nucleus, Nrf2 increases antioxidant gene expression and reduces pro-inflammatory gene expression. By increasing Nrf2 activity, AIMs reduce reactive oxygen species and inflammation in the...

BACKGROUND Air pollution and weather are just two of many environmental factors contributing to traffic accidents (RTA). OBJECTIVES This study assessed the effects of these factors on traffic accidents and related mortalities in Ahvaz, Iran. METHODS In this ecological study, data about RTA, traffic-related mortalities, air pollution (including NO, CO, NO2, NOx PM10, SO2, and O3 rates) and c...

Our functional mapping study of murine gammaherpesvirus 68 (MHV-68, or gammaHV-68) revealed that a mutant harboring a transposon at the ORF49 locus (ORF49(null)) evidenced a highly attenuated in vitro growth. ORF49 resides adjacent to and in an opposite direction from RTA, the primary switch of the gammaherpesvirus life cycle. A FLAG-tagged ORF49 protein was able to transcomplement ORF49(null),...

Ricin A-chain (RTA) and saporin-L1 (SAP) catalyze adenosine depurination of 28S rRNA to inhibit protein synthesis and cause cell death. We present the crystal structures of RTA and SAP in complex with transition state analogue inhibitors. These tight-binding inhibitors mimic the sarcin-ricin recognition loop of 28S rRNA and the dissociative ribocation transition state established for RTA cataly...

Recent studies have shown that cyclosporin A (CsA) may affect ricin A-chain immunotoxin (RTA-IT) therapy. In this study, we evaluated the ability of CsA and its nonirnmunosuppressive analog. SDZ PSC 833, to enhance anti-CD5 T l O l RTA-ITS in vitro. Both 4 pmol/L CsA and 4 pmol/L SDZ PSC 833 significantly and specifically enhanced the cytotoxic activity of T101 RTA-IT on the human lymphoblastic...

BACKGROUND The aim of this study was to investigate the trends in mortality from road traffic accidents (RTA) in Fars Province, southern Iran. METHODS The Age and sex-standardized mortality rate attributed to RTA from 2004 to 2010 in Fars Province was calculated using world standard population. We also used linear regression and chi-squared tests. RESULTS Over the period of study (7 years),...

We analyzed the immediate-early transactivator Rta of Epstein-Barr virus (EBV) for its role as a target for specific cytotoxic T lymphocytes (CTL). Panels of overlapping peptides covering the entire amino acid sequence of Rta were synthesized and used to induce and analyze specific CTL responses in EBV-positive donors. Using peptide-pulsed target cells, we found nine different CTL epitopes that...

Ribosome inactivating proteins (RIPs) depurinate a universally conserved adenine in the α-sarcin/ricin loop (SRL) and inhibit protein synthesis at the translation elongation step. We previously showed that ribosomal stalk is required for depurination of the SRL by ricin toxin A chain (RTA). The interaction between RTA and ribosomes was characterized by a two-step binding model, where the stalk ...

Epstein-Barr virus (EBV) Rta belongs to a lytic switch gene family that is evolutionarily conserved in all gamma-herpesviruses. Emerging evidence indicates that cell cycle arrest is a common means by which herpesviral immediate-early protein hijacks the host cell to advance the virus's lytic cycle progression. To examine the role of Rta in cell cycle regulation, we recently established a doxycy...