BIOBASE Biological Databases / Biologische Datenbanken GmbH,
Halchtersche Strasse 33,
D-38304 Wolfenbüttel
E-mail:
{ulg, spi, cch, mkl, nvo, ewi} @ biobase.de
What reactions and interactions of which molecules lead to cell growth, apoptosis or even cancer, inflammation and other diseases? Following up these questions TRANSPATH provides an information system on regulatory networks of mainly proteinaceous molecules by focusing on signaling pathways involved in the intracellular regulation of transcription factors and genes in mammalian species, mainly human, rat and mouse. The main aim of TRANSPATH is to show the reactions, interactions and connections of specific signaling components.
In TRANSPATH elements of relevant signal transduction pathways can be found, such as ligands, receptors, enzymes and transcription factors, which are stored together with information about their interaction to other signaling molecules
TRANSPATH can be first used for encyclopedic purposes. For researchers and scientists this means that within a short time a huge amount of information can be retrieved, e.g. upon a cellular protein or a specific transcription factor which is involved in signal transduction. The user can start with a word search getting a list of hits. Clicking on a hyperlinked entry from the database a data sheet is retrieved with more detailed information about the specific issue.
A second possible way to work with TRANSPATH is the operative use of our visualization tools. Upon the basis of a large amount of acquired data the user can obtain pathways and networks from reactions and interactions of the molecule of interest in at least four different visualization forms, namely: Cascade, Map, Overview and Shortest Paths. Moreover TRANSPATH offers presently 23 hand-drawn clickable maps from selected pathways.
As an example to present TRANSPATH functionality we show the Wnt-ß-catenin pathway:
The Wnt signaling pathway is conserved in various organisms from worms to mammals where it plays important roles in development, cellular proliferation and differentiation. ß-catenin plays a central role in the transmission of Wnt signals to the nucleus where it stimulates the expression of several target genes (e.g. myc, jun, fra, and cyclin D), and in regulation of cell-cell adhesion by interacting with cadherins. Amount and function of ß-catenin are regulated in different compartments of the cell, e.g. the cytoplasm, cell membrane and the nucleus. In the presence of Wnt signals b-catenin is phosphorylated and thus degraded by proteasomes whereas in the absence of Wnt signals ß-catenin is stabilized and translocated to the nucleus where it binds to transcription factors of the LEF/ TCF family.
As in a number of malignancies (e.g. colon cancer, melanoma, hepatocellular carcinoma, ovarian cancer, endometrial cancer, medulloblastoma pilomatricomas, and prostate cancer) the deregulation of b-catenin signaling has been shown. It is important to learn as much as possible about its regulation and cross-reactions in order to find and create new drugs to treat these diseases.
TRANSPATH provides several search functions for molecules and reactions, such as a keyword search for physiological function or diseases.
The TRANSPATH database preferentially exhibits mammalian - in particular human - molecules and reactions in their healthy appearence.
TRANSPATH will be soon integrated with our other data sources, especially with the TRANSFAC database about transcription factors and their site-specific interactions on DNA leading to expression of specific target genes, which in turn will refer to the intracellular signal transduction network represented in TRANSPATH.
All data in TRANSPATH are extracted and validated from original literature. To keep up with the latest findings in research the data are permanently updated in TRANSPATH.
Furthermore we introduced an evaluation scale: the quality matrix. This evaluation scheme takes into account the origin of the molecules used in the experiments and the methods applied.
Our future perspective is to integrate all databases developed by BIOBASE GmbH to facilitate a recently updated presentation of signaling pathways from an extracellular signal through intracellular signaling molecules down to the level of transcription factors which control the expression of defined target genes. The products of these target genes might then be involved in intra- and extracellular signaling. Last but not least the functionality and guidance through the TRANSPATH operation tools will be continuously improved according to the users needs and new aspects of development.