Identification of inhibitors for the trans-membrane Trypanosoma cruzi eIF2alpha kinase relevant for parasite proliferation

ABSTRACT: We studied the impact of the gene knockout of the TcK2 protein kinase of Trypanosoma cruzi, the causative agent of Chagas disease. TcK2 is structurally similar to the human kinase PERK, which phosphorylates the initiation factor eIF2alpha, and in turn, inhibits translation initiation. As TcK2 kinase promotes parasite proliferation within mammalian cell, it is a potential target for treatment of Chagas disease. Proteomics indicates that proliferative forms express genes including trans-sialidases, normally restricted to infective and non-proliferative trypomastigotes. In addition, TcK2 knockout cells lose phosphorylation of eukaryotic initiation factor 3 and cyclic AMP responsive-like element, recognized to promote growth, likely explaining both decreased proliferation and augmented differentiation.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Trypanosoma Cruzi

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Chagas Disease

SUBMITTER: Sergio Schenkman  

LAB HEAD: Sergio Schenkman

PROVIDER: PXD040597 | Pride | 2023-07-20

REPOSITORIES: Pride