For a long time, proteases were mainly considered as protein degrading enzymes. However, the current view focuses on proteases as signalling molecules [1]. This principle, is clearly exemplified on apoptosis, one of the major mechanisms by which eukaryotic organisms eliminate potentially dangerous, superfluous and damaged cells. Eventhough in this process the caspases were considered to play a central role, more recently, other proteases, in particular the cysteine cathepsins, have also been shown as being important in apoptosis [2]. Initially, the nuclei and the mitochondria were reported to be the key organelles participating in this process. However, more recent data, showed that the lysosomes also play an important role [3].

In order to get an integrative view of the lysosomal pathway of apoptosis, we attempted to build a signalling network using several 'omics' tools.

At the level-1 network, 286 proteins lead to 7729 non-redundant protein-protein interactions. Interestingly, several signalling modules were identified on 243 significant complexes, thus having different molecular functions.

[1] Turk B. Targeting proteases: successes, failures and future prospects. (2006) Nat. Rev. Drug Discov. 5:785-799.

[2] Turk B., Stoka V. (2007) Protease signalling in cell death: caspases versus cysteine cathepsins. FEBS Lett. 581:2761-2767.

[3] Stoka V., Turk V., Turk B. (2007) Lysosomal cysteine cathepsins: signaling pathways in apoptosis. Biol. Chem. 388:555-560.