Expression of recombinant eyestalk crustacean hyperglycemic hormone from the tropical land crab, Gecarcinus lateralis, that inhibits Y-organ ecdysteroidogenesis in vitro.

Crustacean hyperglycemic hormone (CHH) is a pleiotropic neuropeptide that regulates carbohydrate and lipid metabolism, molting, reproduction, and osmoregulation in decapod crustaceans. CHH elevates glucose levels in the hemolymph by stimulating glycogenolysis in target tissues. It also inhibits ecdysteroidogenesis in the molting gland, or Y-organ (YO), possibly as a response to environmental stress.

Determinants that control the specific interactions between TAB1 and p38alpha.

Previous studies have revealed that transforming growth factor-beta-activated protein kinase 1 (TAB1) interacts with p38alpha and induces p38alpha autophosphorylation. Here, we examine the sequence requirements in TAB1 and p38alpha that drive their interaction. Deletion and point mutations in TAB1 reveal that a proline residue in the C terminus of TAB1 (Pro412) is necessary for its interaction with p38alpha.

Frequency and distribution of AP-1 sites in the human genome.

The AP-1-binding sequences are promoter/enhancer elements that play an essential role in the induction of many genes in mammalian cells; however, the number of genes containing AP-1 sites remains unknown. In order to better address the overall effect of AP-1 on expression of genes encoded by the entire genome, a genome-wide analysis of the frequency and distribution of AP-1 sites would be useful; yet to date, no such analysis of AP-1 sites or any other promoter/enhancer elements has been performed. We present here our study of the consensus AP-1 site and two single-bp variants showing that the frequency of AP-1 sites in promoter regions is significantly lower than their average rate of occurrence in the whole genomic sequence, as well as the frequency of a random heptanucleotide suggesting that nature has selected for a decrease in the frequency of AP-1 sites in the regulatory regions of genes.

Distinct roles of basal steady-state and induced H-ferritin in tumor necrosis factor-induced death in L929 cells.

Tumor necrosis factor (TNF) alpha is a cytokine capable of inducing caspase-dependent (apoptotic) cell death in some cells and caspase-independent (necrosis-like) cell death in others. Here, using a mutagenesis screen for genes critical in TNF-induced death in L929 cells, we have found that H-ferritin deficiency is responsible for TNF resistance in a mutant line and that, upon treatment with TNF, this line fails to elevate levels of labile iron pool (LIP), critical for TNF-induced reactive oxygen species (ROS) production and ROS-dependent cell death. Since we found that TNF-induced LIP in L929 cells is primarily furnished by intracellular storage iron, the lesser induction of LIP in H-ferritin-deficient cells results from a reduction of intracellular iron storage caused by less H-ferritin.

Identification of eight genes that are potentially involved in tamoxifen sensitivity in breast cancer cells.

Although the antiestrogen agent tamoxifen has long been used to treat women with hormone receptor positive invasive breast carcinoma, the mechanisms of its action and acquired resistance to tamoxifen during treatment are largely unknown. A number of studies have revealed that over-activation of some signaling pathways can cause tamoxifen resistance; however, very little information is available regarding the genes whose loss-of-function alternation contribute to tamoxifen resistance. Here we used a forward genetic approach in vitro to generate tamoxifen resistant cells from the tamoxifen sensitive breast cancer cell line ZR-75-1, and further identified the disrupted gene in different tamoxifen resistant clones.

Involvement of microRNA in AU-rich element-mediated mRNA instability.

AU-rich elements (AREs) in the 3' untranslated region (UTR) of unstable mRNAs dictate their degradation. An RNAi-based screen performed in Drosophila S2 cells has revealed that Dicer1, Argonaute1 (Ago1) and Ago2, components involved in microRNA (miRNA) processing and function, are required for the rapid decay of mRNA containing AREs of tumor necrosis factor-alpha. The requirement for Dicer in the instability of ARE-containing mRNA (ARE-RNA) was confirmed in HeLa cells.

Activation and signaling of the p38 MAP kinase pathway.

The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve as a nexus for signal transduction and play a vital role in numerous biological processes. In this review, we highlight the known characteristics and components of the p38 pathway along with the mechanism and consequences of p38 activation.