Showing papers by "Tewis Bouwmeester published in 2004"

A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway.

Abstract: Signal transduction pathways are modular composites of functionally interdependent sets of proteins that act in a coordinated fashion to transform environmental information into a phenotypic response. The pro-inflammatory cytokine tumour necrosis factor (TNF)-α triggers a signalling cascade, converging on the activation of the transcription factor NF-κB, which forms the basis for numerous physiological and pathological processes. Here we report the mapping of a protein interaction network around 32 known and candidate TNF-α/NF-κB pathway components by using an integrated approach comprising tandem affinity purification, liquid-chromatography tandem mass spectrometry, network analysis and directed functional perturbation studies using RNA interference. We identified 221 molecular associations and 80 previously unknown interactors, including 10 new functional modulators of the pathway. This systems approach provides significant insight into the logic of the TNF-α/NF-κB pathway and is generally applicable to other pathways relevant to human disease.

Modular decomposition of protein-protein interaction networks

Abstract: We introduce an algorithmic method, termed modular decomposition, that defines the organization of protein-interaction networks as a hierarchy of nested modules. Modular decomposition derives the logical rules of how to combine proteins into the actual functional complexes by identifying groups of proteins acting as a single unit (sub-complexes) and those that can be alternatively exchanged in a set of similar complexes. The method is applied to experimental data on the pro-inflammatory tumor necrosis factor-α (TNF-α)/NFκB transcription factor pathway.