The metacaspases of Trypanosoma cruzi: screening of interactors and search for natural substrates

BOUVIER, L. A.; NIEMIROWICZ, G.T.; SALAS SURDUY, E.; PÉREZ, B.; CAZZULO, J.J.; ALVAREZ, V.E.

Buenos Aires

Otro; SAIB 2013. Argentine Society for Biochemistry and Molecular Biology scientific meeting. ?Molecular mechanisms in cell signaling and gene expression?.; 2013

Apoptosis is a programmed cell death essential for the development and homeostasis in multicellular organisms.  In unicellular organisms, on the other hand, its existence and possible role is still controversial.  Despite the presence of morphological characteristics compatible with apoptosis, caspase orthologs are absent in the sequenced genomes of these organisms. About a decade ago, sequences with some similarity to those of caspases were identified in the genomes of plants, fungi and protozoans and named metacaspases.  This seemed to end the controversy, but doubts arised again when it was shown that these enzymes have biochemical characteristics very different, although they seem to share with caspases some functions, including the regulation of cell cycle and death. Knowledge of the mechanism of action of metacaspases is still very limited, mostly because the targets of their activity are still unknown.  We are searching for natural substrates of T. cruzi metacaspases, by two strategies:  1)  the screening of a number of interactors (obtained by co-purification from parasite extracts and identified by MS), expecting that some of them will be true substrates, and 2) a detailed study of substrate specificity using a peptide library obtained by a new technique called PICS, which should give us valuable information of the consensus sequence recognized by these proteinases.