title: Identification of a developmentally regulated cysteine protease of Trypanosoma brucei.
abstract: Trypanosoma brucei undergoes dramatic metabolic changes during differentiation from the mammalian bloodstream form into the procyclic form of the insect midgut. Because modulation of protein degradation is likely to be important during this process we studied T. brucei for life cycle mediated proteolysis. We detected an increase in the activity of a 28 kDa protease as pleomorphic GUTat 3.1 trypanosomes differentiate in the mammalian bloodstream from long slenders into short stumpies. Short stumpy trypanosomes hydrolyse z-Phe-Arg-AMC 12 fold more actively than either long slenders or procyclics. The 28 kDa protease is activated by dithiothreitol and is inhibited by trans-epoxysuccinyl-L-leucyl-amido(4-guanidino) butane (E-64), indicating that it is a cysteine protease. The proteolytic activity of monomorphic ILTat 1.4 trypanosomes does not increase during mammalian parasitemia. If monomorphic ILTat 1.4 trypanosomes are induced to differentiate into short stumpies by exposure to difluoromethylornithine, however, the activity of the 28 kDa cysteine protease increases 8 fold. This suggests that polyamine depletion induces the 28 kDa cysteine protease and that its expression may be regulated by mechanism not previously described in protozoa.
authors.affiliation: Department of Medicine, University of California, San Diego.
authors.forename: E G
authors.initials: EG
authors.lastname: Pamer
authors.forename: M
authors.initials: M
authors.lastname: So
authors.forename: C E
authors.initials: CE
authors.lastname: Davis
mesh_terms: D000818:Animals; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D004586:Electrophoresis / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D051379:Mice; D008970:Molecular Weight; D009024:Morphogenesis; D014346:Trypanosoma brucei brucei / Q000201:enzymology / Q000254:growth & development*
chemical_list: D003546:Cysteine Endopeptidases; D004229:Dithiothreitol