The Ubiquitin-Proteasome Pathway Plays an Essential Role in Proteolysis during Trypanosoma cruzi Remodeling

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• 作者：Juana L. de Diego ; Jeffrey M. Katz ; Patricia Marshall ; Bessy Gutié ; rrez ; Jerry E. Manning ; Victor Nussenzweig ; and Jorge Gonzá ; lez
• 刊名：Biochemistry
• 出版年：2001
• 出版时间：January 30, 2001
• 年：2001
• 卷：40
• 期：4
• 页码：1053 - 1062
• 全文大小：176K
• 年卷期：v.40,no.4(January 30, 2001)
• ISSN：1520-4995

文摘

Here, we document for the first time the presence of the 26S proteasome and the ubiquitinpathway in a protozoan parasite that is in an early branch in the eukaryotic lineage. The 26S proteasomeof Trypanosoma cruzi epimastigotes was identified as a high molecular weight complex (1400 kDa) withan ATP-dependent chymotrypsin-like activity against the substrate Suc-LLVY-Amc. This activity wasinhibited by proteasome inhibitors and showed same electrophorectic migration pattern as yeast 26Sproteasome in nondenaturating gels. About 30 proteins in a range of 25-110 kDa were detected in thepurified T. cruzi 26S proteasome. Antibodies raised against the AAA family of ATPases from eukaryotic26S proteasome and the T. cruzi 20S core specifically recognized components of T. cruzi 26S. To confirmthe biological role of 26S in this primitive eukaryotic parasite, we analyzed the participation of the ubiquitin(Ub)-proteasome system in protein degradation during the time of parasite remodeling. Protein turnoverin trypomastigotes was proteasome and ATP-dependent and was enhanced during the transformation ofthe parasites into amastigotes. If 20S proteasome activity is inhibited, ubiquitinated proteins accumulatein the parasites. As expected from the profound morphological changes that occur during transformation,cytoskeletal proteins associated with the flagellum are targets of the ubiquitin-proteasome pathway.