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The protein partners of GTP cyclohydrolase I in rat organs. PLoS One 2012;7(3):e33991



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OBJECTIVE: GTP cyclohydrolase I (GCH1) is the rate-limiting enzyme for tetrahydrobiopterin biosynthesis and has been shown to be a promising therapeutic target in ischemic heart disease, hypertension, atherosclerosis and diabetes. The endogenous GCH1-interacting partners have not been identified. Here, we determined endogenous GCH1-interacting proteins in rat.

METHODS AND RESULTS: A pulldown and proteomics approach were used to identify GCH1 interacting proteins in rat liver, brain, heart and kidney. We demonstrated that GCH1 interacts with at least 17 proteins including GTP cyclohydrolase I feedback regulatory protein (GFRP) in rat liver by affinity purification followed by proteomics and validated six protein partners in liver, brain, heart and kidney by immunoblotting. GCH1 interacts with GFRP and very long-chain specific acyl-CoA dehydrogenase in the liver, tubulin beta-2A chain in the liver and brain, DnaJ homolog subfamily A member 1 and fatty aldehyde dehydrogenase in the liver, heart and kidney and eukaryotic translation initiation factor 3 subunit I (EIF3I) in all organs tested. Furthermore, GCH1 associates with mitochondrial proteins and GCH1 itself locates in mitochondria.

CONCLUSION: GCH1 interacts with proteins in an organ dependant manner and EIF3I might be a general regulator of GCH1. Our finding indicates GCH1 might have broader functions beyond tetrahydrobiopterin biosynthesis.

Author List

Du J, Teng RJ, Lawrence M, Guan T, Xu H, Ge Y, Shi Y


Ru-Jeng Teng MD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acyl-CoA Dehydrogenase, Long-Chain
Cell Line
Eukaryotic Initiation Factor-3
GTP Cyclohydrolase
Intracellular Signaling Peptides and Proteins
Multiprotein Complexes
Protein Binding
Protein Interaction Mapping
Protein Transport
Rats, Sprague-Dawley
Reproducibility of Results
Retinal Dehydrogenase
jenkins-FCD Prod-478 d1509cf07a111124a2d122fd3df854cc0b993c00