Proteomics

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Secreted parasite Pin1 isomerase stabilizes host PKM2 to reprogram host cell metabolism


ABSTRACT: Metabolic reprogramming is an important feature of host-pathogen interactions and a hallmark of tumorigenesis. The intracellular apicomplexa parasite Theileria induces a Warburg-like effect in host leukocytes by hijacking signaling machineries, epigenetic regulators and transcriptional programs to create a transformed cell state. The molecular mechanisms underlying host cell transformation are unknown. Here we show that a parasite-encoded prolyl-isomerase, TaPin1, stabilizes host pyruvate kinase isoform M2 (PKM2) leading to HIF-1α-dependent regulation of metabolic enzymes, glucose uptake and transformed phenotypes in parasite-infected cells. Our results provide a direct molecular link between the secreted parasite TaPin1 protein and host gene expression programs. This study demonstrates the importance of prolyl isomerization in the parasite manipulation of host metabolism.

INSTRUMENT(S): LTQ Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Fibroblast

SUBMITTER: Justine Marsolier  

LAB HEAD: Jonathan WEITZMAN

PROVIDER: PXD012895 | Pride | 2019-11-13

REPOSITORIES: Pride

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Secreted parasite Pin1 isomerase stabilizes host PKM2 to reprogram host cell metabolism.

Marsolier Justine J   Perichon Martine M   Weitzman Jonathan B JB   Medjkane Souhila S  

Communications biology 20190430


Metabolic reprogramming is an important feature of host-pathogen interactions and a hallmark of tumorigenesis. The intracellular apicomplexa parasite <i>Theileria</i> induces a Warburg-like effect in host leukocytes by hijacking signaling machineries, epigenetic regulators and transcriptional programs to create a transformed cell state. The molecular mechanisms underlying host cell transformation are unclear. Here we show that a parasite-encoded prolyl-isomerase, TaPin1, stabilizes host pyruvate  ...[more]

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