TLS, EWS and TAF15: a model for transcriptional integration of gene expression.

Multifunctional proteins are demonstrating that gene expression is not a series of compartmentalized events beginning with transcription and culminating in delivery of mature mRNA into the cytoplasm, but an integrated pathway of transcription, splicing, RNA metabolism and subcellular targeting of translation. One such multifunctional family is made up of the RNA-binding proteins TLS, EWS and TAF15. These three proteins each contribute a potent transcriptional activation domain to oncogenic fusion proteins, and the formation of these fusion genes are thought to be the primary causes of their associated cancers. Wild-type TLS, EWS and TAF15 can function as classical transcription factors in addition to their better-known functions in splicing and mRNA transport. The interaction between TLS and the stress-response protein YB-1 is an example of how these proteins can induce a multi-faceted change in gene expression, as they can interact to induce changes in both transcription and splicing of target genes. Investigating the multiple functions of TLS, EWS and TAF15 will enhance our understanding of gene expression as a whole, and also allow us to better understand how these proteins may be contributing to the oncogenic pathways the associated fusion proteins initiate.

Peptide-based approaches to treat asthma, arthritis, other autoimmune diseases and pathologies of the central nervous system.

In this review we focus on peptide- and peptidomimetic-based approaches that target autoimmune diseases and some pathologies of the central nervous system. Special attention is given to asthma, allergic rhinitis, osteoarthritis, and Alzheimer's disease, but other related pathologies are also reviewed, although to a lesser degree. Among others, drugs like Diacerhein and its active form Rhein, Pralnacasan, Anakinra (Kineret), Omalizumab, an antibody "BION-1", directed against the common beta-chain of cytokine receptors, are described below as well as attempts to target beta-amyloid peptide aggregation. Parts of the review are also dedicated to targeting of pathologic conditions in the brain and in other tissues with peptides as well as methods to deliver larger molecules through the "blood--brain barrier" by exploring receptor-mediated transport, or elsewhere in the body by using peptides as carriers through cellular membranes. In addition to highlighting current developments in the field, we also propose, for future drug targets, the components of the inflammasome protein complex, which is believed to initiate the activation of caspase- 1 dependent signaling events, as well as other pathways that signal inflammation. Thus we discuss the possibility of targeting inflammasome components for negative or positive modulation of an inflammatory response.