Proteasome activity is required for the stage-specific transformation of a protozoan parasite.
Cysteine Endopeptidases
Proteasome Endopeptidase Complex
03 medical and health sciences
0302 clinical medicine
Dose-Response Relationship, Drug
Multienzyme Complexes
Trypanosoma cruzi
Animals
Cell Differentiation
Cysteine Proteinase Inhibitors
Acetylcysteine
DOI:
10.1084/jem.184.5.1909
Publication Date:
2004-06-24T07:56:10Z
AUTHORS (8)
ABSTRACT
A prominent feature of the life cycle of intracellular parasites is the profound morphological changes they undergo during development in the vertebrate and invertebrate hosts. In eukaryotic cells, most cytoplasmic proteins are degraded in proteasomes. Here, we show that the transformation in axenic medium of trypomastigotes of Trypanosoma cruzi into amastigote-like organisms, and the intracellular development of the parasite from amastigotes into trypomastigotes, are prevented by lactacystin, or by a peptide aldehyde that inhibits proteasome function. Clasto-lactacystin, an inactive analogue of lactacystin, and cell-permeant peptide aldehyde inhibitors of T. cruzi cysteine proteinases have no effect. We have also identified the 20S proteasomes from T. cruzi as a target of lactacystin in vivo. Our results document the essential role of proteasomes in the stage-specific transformation of a protozoan.
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