Basic and clinical proteomics from the EU Health Research perspective.

The European Union (EU) is one of the main public funders of research in Europe and its major instrument for funding is the Seventh Framework Programme for research and technological development (FP7). The bulk of funding in FP7 goes to collaborative research, with the objective of establishing excellent research projects and networks. Understanding the functions of proteins is essential for the rational development of disease prevention, diagnosis and treatment, therefore the EU has largely invested in proteomics, in particular for technology development, data standardisation and sharing efforts, and the application of proteomics in the clinic. The scientific community, including both academia and industry, is encouraged to apply for FP7 funding so that the EU can even more efficiently support innovative health research and ultimately, bring better healthcare to patients.

Europe combating cancer: the European Union's commitment to cancer research in the 6th Framework Programme.

As one of the major health issues in Europe, cancer was a research priority in the 6th Framework Programme (2002-2006). About 485 million euros were devoted to this theme, which allowed funding of 108 multidisciplinary transnational projects. A significant part of them was large-scale initiatives addressing complex issues through a broad combination of competences. All major types of cancer were covered, as well as the three dimensions such as prevention, diagnostic and treatment, with a particular emphasis on translational research aiming at bringing basic knowledge on medical practice. This approach will be continued in the 7th Framework Programme (2007-2013), together with a strengthened effort to improve the coordination of European cancer research, which is fragmented and in which EU action represents only a small part. EU cancer research will also be addressed within the reinforced efforts in the areas of pharmaceutical and technological developments as well as common aetiological mechanisms of diseases that the 7th Framework Programme will undertake.

Cloning and sequencing of a novel metallothionein gene in Mytilus galloprovincialis Lam.

Metallothionein (MT) is a ubiquitous, metal-inducible protein with an important role in the homeostasis and in the detoxification of heavy metals. This work reports the cloning and sequencing of a MT gene encoding a MT isoform (MT20-IIIa) in the mussel Mytilus galloprovincialis Lam, a lamellibranch mollusc known to accumulate and to detoxify large amounts of metal. The MT gene, lacking the 5' promoter region, is 1865 bp long and has a tripartite structure consisting of three exons and two introns. The putative open reading frame (ORF) encodes a polypeptide of 72 amino acids, which corresponds to the MT-I class, type 2 family (http://www.unizh.ch/~mtpage/classif.html). The structure of the gene and the putative MT20-III protein have been compared with those of other species. The putative biological significance of the differences at the amino acid level among the different MTs is discussed.

Functional regulation of semaphorin receptors by proprotein convertases.

PLEXIN genes encode receptors for secreted and membrane-bound semaphorins. It was proposed that the extracellular domain of plexins acts as an inhibitory moiety, preventing receptor activation. Here we show that plexin-B1 and plexin-B2 undergo proteolytic processing in their extracellular portion, thereby converting single-chain precursors into non-disulfide-linked, heterodimeric receptors. We demonstrate that plexin processing is mediated by subtilisin-like proprotein convertases, by inhibition with alpha1-antitrypsin Portland, and by mutagenesis of the substrate-cleavage sites. We provide evidence indicating that proprotein convertases cleave plexins in a post-Golgi compartment and, likely, at the cell surface. In addition, we find that both cell surface targeting and proteolytic processing of plexin-B1 depend on protein-protein interaction motifs in the cytoplasmic domain of the receptor. We then show that proteolytic conversion of plexin-B1 into a heterodimeric receptor greatly increases the binding and the functional response to its specific ligand semaphorin 4D/CD100. Thus, we conclude that cleavage by proprotein convertases is a novel regulatory step for semaphorin receptors localized at the cell surface.