ArticleJournal of molecular biology2008
Protein quaternary structure and expression levels contribute to peroxisomal-targeting-sequence-1-mediated peroxisomal import of human soluble epoxide hydrolase.
Article in Journal of molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- The mammalian peroxisomal membrane is permeable to both GSH and GSSG - Implications for intraperoxisomal redox homeostasis.Redox biology · 2023Article
- Dimerization Drives Proper Folding of Human Alanine:Glyoxylate Aminotransferase But Is Dispensable for Peroxisomal Targeting.Journal of personalized medicine · 2021Article
- Pnc1 piggy-back import into peroxisomes relies on Gpd1 homodimerisation.Scientific reports · 2017Article
- Peroxisome biogenesis disorders.Translational science of rare diseases · 2016Article
- Article
- Peroxisomal translocation of soluble epoxide hydrolase protects against ischemic stroke injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2015Article
- Soluble Epoxide Hydrolase Deficiency or Inhibition Attenuates MPTP-Induced Parkinsonism.Molecular neurobiology · 2015Article
- The peroxisomal protein import machinery displays a preference for monomeric substrates.Open biology · 2015Article
- Peroxisomal Import Reduces the Proapoptotic Activity of Deubiquitinating Enzyme USP2.PloS one · 2015Article
- Redox interplay between mitochondria and peroxisomes.Frontiers in cell and developmental biology · 2015Review
- Role of soluble epoxide hydrolase in age-related vascular cognitive decline.Prostaglandins & other lipid mediators · 2014Article
- Effect of soluble epoxide hydrolase polymorphism on substrate and inhibitor selectivity and dimer formation.Journal of lipid research · 2014Article
- Dual targeting of peroxisomal proteins.Frontiers in physiology · 2013Review
- Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health.Annual review of pharmacology and toxicology · 2013Review
- Molecular requirements for peroxisomal targeting of alanine-glyoxylate aminotransferase as an essential determinant in primary hyperoxaluria type 1.PLoS biology · 2012Article
- PEX5 protein binds monomeric catalase blocking its tetramerization and releases it upon binding the N-terminal domain of PEX14.The Journal of biological chemistry · 2011Article
- Article
- Opposite regulation of cholesterol levels by the phosphatase and hydrolase domains of soluble epoxide hydrolase.The Journal of biological chemistry · 2008Article
- Predicted mouse peroxisome-targeted proteins and their actual subcellular locations.BMC bioinformatics · 2008Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The peroxisomal targeting sequence 1 (PTS1) is a consensus tripeptide 1 (S/C/A)(K/R/H)(L/M) that is found at the C-terminus of most peroxisomal proteins. However, the only known mammalian protein containing a terminal methionine PTS1 (SKM), human soluble epoxide hydrolase (hsEH), shows both peroxisomal and cytosolic localizations in vivo. Mechanisms regulating the subcellular localization of hsEH thus remain unclear. Here we utilized green fluorescent protein-hsEH fusion constructs to study the peroxisomal targeting of hsEH in transiently and stably transfected Chinese hamster ovary cells. Our results suggest that the peroxisomal import of hsEH is regulated by three factors. First, we show that SKM is required, but not sufficient, for peroxisomal import. Second, by manipulating protein expression levels, we show that SKM mediates peroxisomal import of wild-type hsEH only when expression levels are high. Third, we show that amino acid modifications that decrease subunit oligomerization and presumably enhance accessibility of the SKM motif confer peroxisomal targeting even at low protein expression levels. We conclude that, in hsEH, SKM is a necessary but inefficient and context-dependent PTS1. Peroxisomal import occurs when expression levels are high or when the SKM motif is accessible. These results provide a mechanistic basis for understanding the cell-specific and tissue-specific localization of hsEH in vivo.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.