7 research outputs found
Uniformly curated signaling pathways reveal tissue-specific cross-talks and support drug target discovery
Motivation: Signaling pathways control a large variety of cellular processes.
However, currently, even within the same database signaling pathways are often
curated at different levels of detail. This makes comparative and cross-talk
analyses difficult. Results: We present SignaLink, a database containing 8
major signaling pathways from Caenorhabditis elegans, Drosophila melanogaster,
and humans. Based on 170 review and approx. 800 research articles, we have
compiled pathways with semi-automatic searches and uniform, well-documented
curation rules. We found that in humans any two of the 8 pathways can
cross-talk. We quantified the possible tissue- and cancer-specific activity of
cross-talks and found pathway-specific expression profiles. In addition, we
identified 327 proteins relevant for drug target discovery. Conclusions: We
provide a novel resource for comparative and cross-talk analyses of signaling
pathways. The identified multi-pathway and tissue-specific cross-talks
contribute to the understanding of the signaling complexity in health and
disease and underscore its importance in network-based drug target selection.
Availability: http://SignaLink.orgComment: 9 pages, 4 figures, 2 tables and a supplementary info with 5 Figures
and 13 Table
Stress-induced rearrangements of cellular networks: consequences for protection and drug design
The complexity of the cells can be described and understood by a number of
networks such as protein-protein interaction, cytoskeletal, organelle,
signalling, gene transcription and metabolic networks. All these networks are
highly dynamic producing continuous rearrangements in their links, hubs,
network-skeleton and modules. Here we describe the adaptation of cellular
networks after various forms of stress causing perturbations, congestions and
network damage. Chronic stress decreases link-density, decouples or even
quarantines modules, and induces an increased competition between network hubs
and bridges. Extremely long or strong stress may induce a topological phase
transition in the respective cellular networks, which switches the cell to a
completely different mode of cellular function. We summarize our initial
knowledge on network restoration after stress including the role of molecular
chaperones in this process. Finally, we discuss the implications of
stress-induced network rearrangements in diseases and ageing, and propose
therapeutic approaches both to increase the robustness and help the repair of
cellular networks.Comment: 9 pages, 1 table, 2 figures, invited paper of FEBS Letters Cellular
Stress special issu
The small heat-shock proteins HSPB2 and HSPB3 form well-defined heterooligomers in a unique 3 to 1 subunit ratio
Contains fulltext :
75686.pdf (Publisher’s version ) (Open Access