Identification of Amino Acids in Trm734 Required for 2'--Methylation of the tRNA Wobble Residue.

All organisms methylate their nucleic acids, and this methylation is critical for proper gene expression at both the transcriptional and translational levels. For proper translation in eukaryotes, 2'--methylation of C (Cm) and G (Gm) in the anticodon loop of tRNA is critical, with defects in these modifications associated with human disease. In yeast, Cm is formed by an enzyme that consists of the methyltransferase Trm7 in complex with the auxiliary protein Trm732, and Gm is formed by an enzyme that consists of Trm7 in complex with Trm734.

Identification of a Trm732 Motif Required for 2'--methylation of the tRNA Anticodon Loop by Trm7.

Posttranscriptional tRNA modifications are essential for proper gene expression, and defects in the enzymes that perform tRNA modifications are associated with numerous human disorders. Throughout eukaryotes, 2'--methylation of residues 32 and 34 of the anticodon loop of tRNA is important for proper translation, and in humans, a lack of these modifications results in non-syndromic X-linked intellectual disability. In yeast, the methyltransferase Trm7 forms a complex with Trm732 to 2'--methylate tRNA residue 32 and with Trm734 to 2'--methylate tRNA residue 34.

Identification of the enzymes responsible for m2,2G and acp3U formation on cytosolic tRNA from insects and plants.

Posttranscriptional modification of tRNA is critical for efficient protein translation and proper cell growth, and defects in tRNA modifications are often associated with human disease. Although most of the enzymes required for eukaryotic tRNA modifications are known, many of these enzymes have not been identified and characterized in several model multicellular eukaryotes. Here, we present two related approaches to identify the genes required for tRNA modifications in multicellular organisms using primer extension assays with fluorescent oligonucleotides.

Interleukin-6 receptor enhances early colonization of the murine omentum by upregulation of a mannose family receptor, LY75, in ovarian tumor cells.

One of the earliest metastatic events in human ovarian cancer, tumor spread to the omentum, may be influenced by expression of interleukin 6 (IL6) and its cognate receptor (IL6Rα). Previous reports have shown that IL6 and IL6Rα expression is elevated in the serum and ascites of patients with ovarian cancer and that this can influence in vitro processes such as cell survival, proliferation and migration. In this study, overexpression of IL6Rα, and to a lesser extent IL6, enhanced tumor growth on the omentum.

The syntaxin 4 N terminus regulates its basolateral targeting by munc18c-dependent and -independent mechanisms.

To generate and maintain epithelial cell polarity, specific sorting of proteins into vesicles destined for the apical and basolateral domain is required. Syntaxin 3 and 4 are apical and basolateral SNARE proteins important for the specificity of vesicle fusion at the apical and basolateral plasma membrane domains, respectively, but how these proteins are specifically targeted to these domains themselves is unclear. Munc18/SM proteins are potential regulators of this process.

Differences in wound healing in mice with deficiency of IL-6 versus IL-6 receptor.

IL-6 modulates immune responses and is essential for timely wound healing. As the functions mediated by IL-6 require binding to its specific receptor, IL-6Ralpha, it was expected that mice lacking IL-6Ralpha would have the same phenotype as IL-6-deficient mice. However, although IL-6Ralpha-deficient mice share many of the inflammatory deficits seen in IL-6-deficient mice, they do not display the delay in wound healing.

Expression of soluble interleukin-6 receptor in malignant ovarian tissue.

Objective: The objective of the study was to investigate interleukin-6 receptor (IL6R) isoforms and sheddases in the ovarian tumor microenvironment.

Study Design: Expression of IL6R and sheddases was measured in tissue samples of papillary serous ovarian carcinomas and benign ovaries by real-time polymerase chain reaction and immunohistochemistry. Murine xenograft samples were tested by enzyme-linked immunosorbent assay to discriminate and evaluate tumor and host contributions of IL6R.

In vitro metastatic colonization of human ovarian cancer cells to the omentum.

Despite the potentially crucial contributions of the omentum in the regulation of ovarian cancer metastatic growth, it remains a poorly understood organ. Due to its anatomic location and structural fragility, the omentum presents inherent challenges to mechanism-based in vivo studies. Thus, the availability of an ex vivo omental model would, in part, address some of these difficulties posed.

Toll-like receptor expression in normal ovary and ovarian tumors.

Recent studies have implicated inflammation in the initiation and progression of ovarian cancer, though the mechanisms underlying this effect are still not clear. Toll-like receptors (TLRs) allow immune cells to recognize pathogens and to trigger inflammatory responses. Tumor cell expression of TLRs can promote inflammation and cell survival in the tumor microenvironment.