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

• Published in: Communications biology Vol. 2; no. 1; p. 152
• Main Authors: Marsolier, Justine, Perichon, Martine, Weitzman, Jonathan B., Medjkane, Souhila
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30-04-2019; Nature Publishing Group
• Subjects: 13; 13/1; 13/106; 13/109; 13/31; 13/44; 13/89; 38; 38/39; 38/77; 631/67/2327; 631/80/86; Animals; Antiprotozoal Agents - pharmacology; Biological Transport; Biology; Biomedical and Life Sciences; Carrier Proteins - antagonists & inhibitors; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cattle; Cell Line, Transformed; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Enzyme Inhibitors - pharmacology; Epigenetics; Gene expression; Gene Expression Regulation; Glucose - metabolism; Host-Pathogen Interactions - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Intracellular; Isomerization; Kinases; Leukocytes; Life Sciences; Lymphocytes - drug effects; Lymphocytes - enzymology; Lymphocytes - parasitology; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - genetics; Membrane Proteins - metabolism; Metabolic Networks and Pathways - genetics; Metabolism; Molecular modelling; Naphthoquinones - pharmacology; NIMA-Interacting Peptidylprolyl Isomerase - antagonists & inhibitors; NIMA-Interacting Peptidylprolyl Isomerase - genetics; NIMA-Interacting Peptidylprolyl Isomerase - metabolism; Parasites; Phenotypes; Pin1 protein; Protozoan Proteins - antagonists & inhibitors; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Pyruvate kinase; Pyruvic acid; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Signal Transduction; Theileria - drug effects; Theileria - enzymology; Theileria - genetics; Theileria - growth & development; Thyroid Hormone-Binding Proteins; Thyroid Hormones - genetics; Thyroid Hormones - metabolism; Transcription; Tumorigenesis; Cell signalling; Cancer metabolism
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-019-0386-6

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 unclear. 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.
Marsolier et al. show that a parasite-encoded prolyl-isomerase, TaPin1, stabilizes host pyruvate kinase isoform M2 (PKM2), leading to metabolically transformed phenotypes in parasite-infected cells. This study illustrates how intracellular parasites use prolyl isomerization to manipulate host metabolism to their advantage.