A Bioinformatics Resource for TWEAK-Fn14 Signaling Pathway

Abstract

TNF-related weak inducer of apoptosis (TWEAK) is a new member of the TNF superfamily. It signals through TNFRSF12A, commonly known as Fn14. The TWEAK-Fn14 interaction regulates cellular activities including proliferation, migration, differentiation, apoptosis, angiogenesis, tissue remodeling and inflammation. Although TWEAK has been reported to be associated with autoimmune diseases, cancers, stroke, and kidney-related disorders, the downstream molecular events of TWEAK-Fn14 signaling are yet not available in any signaling pathway repository. In this paper, we manually compiled from the literature, in particular those reported in human systems, the downstream reactions stimulated by TWEAK-Fn14 interactions. Our manual amassment of the TWEAK-Fn14 pathway has resulted in cataloging of 46 proteins involved in various biochemical reactions and TWEAK-Fn14 induced expression of 28 genes. We have enabled the availability of data in various standard exchange formats from NetPath, a repository for signaling pathways. We believe that this composite molecular interaction pathway will enable identification of new signaling components in TWEAK signaling pathway. This in turn may lead to the identification of potential therapeutic targets in TWEAK-associated disorders.

Figure 1

Workflow of the study. Articles were screened based on TWEAK stimulus and the molecular events were added to PathBuilder. Data were then transferred to NetPath repository. With the help of PathVisio tool, the reactions were used to generate the TWEAK signaling map (http://www.netpath.org/netslim/tweak_pathway.html).

Figure 2

Illustration of the TWEAK page in NetPath. The image provides an outline of the TWEAK pathway as visualized in the NetPath webpage. The figure shows the statistical details of TWEAK pathway-based reactions (right upper corner). Under, “Molecules involved in TWEAK signaling pathway”, each molecule has been linked to its respective NetPath page. Tabs have been provided which leads to the details of the “pathway authority,” “curators,” and “comments” tab—where the users can provide their feedback and the reaction tabs. “Access to data” indicates links to the events regulated by TWEAK. The pathway can be downloaded from the three standard formats provided at the bottom of the page.

Figure 3

TWEAK signaling pathway: illustration of the TWEAK signaling pathway as visualized in NetSlim web page. Each molecule is linked to its corresponding page in NetPath. Each reaction is linked to its respective PubMed citation. Dashed arrows represent the downstream reactions leading to the corresponding events while the solid arrows indicate the direct association between the indicated molecules. Gene symbol(s) has been used to denote proteins in the pathway map (refer to Synonymous for common names).