ArticleThe Journal of biological chemistry2010
Toxoplasma gondii activates hypoxia-inducible factor (HIF) by stabilizing the HIF-1alpha subunit via type I activin-like receptor kinase receptor signaling.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 66 citations in OpenAlex.
- The mevalonate and methylerythritol phosphate pathways as therapeutic targets in protozoan parasites: from moonlighting enzymes to metabolic plasticity.Cell communication and signaling : CCS · 2026Review
- Intravitreal Administration of a Selective HDAC6 Inhibitor Prevents Retinal Damage Progression in the Acute Ocular Toxoplasmosis Model.ACS infectious diseases · 2026Article
- GSK3β/HIF-1α signaling-dependent anti-parasite effect ofiScience · 2026Article
- Neospora caninum hijacks host PFKFB3-driven glycolysis to facilitate intracellular propagation of parasites.Veterinary research · 2025Article
- Hypoxia and collagen deposition in the kidneys infected with Acanthamoeba sp.Scientific reports · 2024Article
- The Toxoplasma gondii F-Box Protein L2 Functions as a Repressor of Stage Specific Gene Expression.PLoS pathogens · 2024Article
- Article
- Article
- Identification ofmSphere · 2023Article
- Regulatory Functions of Hypoxia in Host-Parasite Interactions: A Focus on Enteric, Tissue, and Blood Protozoa.Microorganisms · 2023Review
- Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases.Frontiers in immunology · 2023Article
- An image-based high-content screening for compounds targetingFrontiers in cellular and infection microbiology · 2023Article
- Article
- Assessment of selected molecular factors and 17-β estradiol dosage in response toVeterinary world · 2022Article
- Transcription Factors Interplay Orchestrates the Immune-Metabolic Response ofFrontiers in cellular and infection microbiology · 2021Review
- Repurposing bioenergetic modulators against protozoan parasites responsible for tropical diseases.International journal for parasitology. Drugs and drug resistance · 2020Article
- Transcriptional Analyses Identify Genes That Modulate Bovine Macrophage Response toFrontiers in cellular and infection microbiology · 2020Article
- Cryptosporidium parvum alters glucose transport mechanisms in infected enterocytes.Parasitology research · 2019Article
- The HIF-1α/LC3-II Axis Impacts Fungal Immunity in Human Macrophages.Infection and immunity · 2019Article
- Toxoplasma F-box protein 1 is required for daughter cell scaffold function during parasite replication.PLoS pathogens · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Toxoplasma gondii is an intracellular protozoan parasite that can cause devastating disease in fetuses and immune-compromised individuals. We previously reported that the alpha subunit of the host cell transcription factor, hypoxia-inducible factor-1 (HIF-1), is up-regulated by infection and necessary for Toxoplasma growth. Under basal conditions, HIF-1alpha is constitutively expressed but rapidly targeted for proteasomal degradation after two proline residues are hydroxylated by a family of prolyl hydroxylases (PHDs). The PHDs are alpha-ketoglutarate-dependent dioxygenases that have low K(m) values for oxygen, making them important cellular oxygen sensors. Thus, when oxygen levels decrease, HIF-1alpha is not hydroxylated, and HIF-1 is activated. How Toxoplasma activates HIF-1 under normoxic conditions remains unknown. Here, we report that Toxoplasma infection increases HIF-1alpha stability by preventing HIF-1alpha prolyl hydroxylation. Infection significantly decreases PHD2 abundance, which is the key prolyl hydroxylase for regulating HIF-1alpha. The effects of Toxoplasma on HIF-1alpha abundance and prolyl hydroxylase activity require activin-like receptor kinase signaling. Finally, parasite growth is severely diminished when signaling from this family of receptors is inhibited. Together, these data indicate that PHD2 is a key host cell factor for T. gondii growth and represent a novel mechanism by which a microbial pathogen subverts host cell signaling and transcription to establish its replicative niche.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.