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In brief: May 2003Chromosome Dynamics
Role of Polo-like kinase CDC5 in programming meiosis I chromosome segregation
A distinct programme of chromosome segregation occurs during meiosis. Lee and Amon investigated the role of the yeast Polo-like kinase CDC5 and found it to be a key regulator of meiosis I. It was required: at the onset of anaphase I to phosphorylate and remove cohesin from chromosome arms; during meiosis I to co-orientate sister kinetochores by phosphorylating Mam1; and to release Cdc14 from the nucleolus and for spindle assembly during anaphase I. T-Cell Signalling
SWAP-70-like adapter of T cells, an adapter protein that regulates early TCR-initiated signaling in TH2 lineage cells
Here, Tanaka et al. describe the identification of SWAP70-like adaptor of T cells (SLAT), a protein that is selectively expressed at high levels by T helper 2 (TH2) cells but not TH1 cells. SLAT positively regulates IL-4 expression and negatively regulates IFN- Cell Death And Immunity
Essential role for caspase 8 in T-cell mediated homeostasis and T-cell mediated immunity
The role of caspase-8 in immunity is uncertain as disruption of the gene is lethal during embryogenesis. In this new study, mice with a T-cell-specific caspase deficiency were shown to have normal thymic output of T cells but decreased numbers of peripheral T cells. T-cell clonal expansion was also impaired — apparently owing to reduced survival rather than a defect in T-cell activation — and the mice were unable to mount effective anti-viral responses. Immunotherapy
Nonredundant roles of antibody, cytokines, and perforin in the eradication of established Her-2/neu carcinomas
A DNA vaccine that encodes ERBB2 (also known as HER2/neu) has been shown to stimulate immune rejection of established breast tumours in mice. Curcio et al. analysed this mechanism and showed that successful immunotherapy requires the actions of CD4+ and CD8+ T cells, CD1d-restricted natural-killer T cells, neutrophils, macrophages, antibodies, Fc receptors, IFN- Kinase Inhibitors
Kinase inhibitors: not just for kinases anymore
Small-molecule kinase inhibitors are widely used as tools for understanding the physiological roles of particular kinases and as leads for drug design; however, their use is often complicated by their lack of specificity. Although this can partly be accounted for by the similarity of the ATP-binding site between kinases, some kinase inhibitors also inhibit enzymes not known to bind ATP. The authors show that for several widely used kinase inhibitors, their nonspecificity could be due to the formation of aggregates, and so results obtained from the use of these compounds should be interpreted cautiously. Anti-obesity Drugs
Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase
Acetyl-coenzyme A carboxylases (ACCs), which regulate fatty acid biosynthesis, are a possible target for anti-obesity drugs. The carboxy-terminal (CT) domain of ACCs is also the target of several herbicides. Zhang et al. determined the structure of the CT domain of an ACC from yeast, and identified the probable area of the active site targeted by herbicides, thereby providing a starting point for the development of inhibitors of human ACCs. | |
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expression. After antigen stimulation of the T-cell receptor (TCR) SLAT translocates to the immunological synapse, where it associates with the tyrosine kinase ZAP70. Transient overexpression of SLAT caused reduced association of ZAP70 with TCR
and interfered with ZAP70, but not LCK, signalling. This study indicates a role for SLAT in the differentiation, activation and/or expansion of TH2 cells, but further studies are required to elucidate the mechanisms by which it acts.