ArticleProceedings of the National Academy of Sciences of the United States of America2002
Regulation of transferrin-mediated iron uptake by HFE, the protein defective in hereditary hemochromatosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 146 citations in OpenAlex.
- Loss of Hfe impairs hematopoietic stem and progenitor cell function.Blood. Red cells & iron · 2026Article
- HFE-Related Hemochromatosis May Be a Primary Kupffer Cell Disease.Biomedicines · 2025Review
- Cerebrospinal fluid β2-microglobulin promotes the tau pathology through microglia-astrocyte communication in Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Oral iron therapy: Current concepts and future prospects for improving efficacy and outcomes.British journal of haematology · 2024Review
- Elevated transferrin receptor impairs T cell metabolism and function in systemic lupus erythematosus.Science immunology · 2023Article
- Discovery of a Transferrin Receptor 1-Binding Aptamer and Its Application in Cancer Cell Depletion for Adoptive T-Cell Therapy Manufacturing.Journal of the American Chemical Society · 2022Article
- The hemochromatosis protein HFE 20 years later: An emerging role in antigen presentation and in the immune system.Immunity, inflammation and disease · 2017Review
- Brain Iron Metabolism Dysfunction in Parkinson's Disease.Molecular neurobiology · 2017Review
- Metal Dyshomeostasis and Their Pathological Role in Prion and Prion-Like Diseases: The Basis for a Nutritional Approach.Frontiers in neuroscience · 2017Review
- HFE Variants and the Expression of Iron-Related Proteins in Breast Cancer-Associated Lymphocytes and Macrophages.Cancer microenvironment : official journal of the International Cancer Microenvironment Society · 2016Article
- Decreased ferroportin promotes myeloma cell growth and osteoclast differentiation.Cancer research · 2015Article
- Differential effects of basolateral and apical iron supply on iron transport in Caco-2 cells.Genes & nutrition · 2015Article
- Targeting therapeutics across the blood brain barrier (BBB), prerequisite towards thrombolytic therapy for cerebrovascular disorders-an overview and advancements.AAPS PharmSciTech · 2015Review
- HFE gene variants, iron, and lipids: a novel connection in Alzheimer's disease.Frontiers in pharmacology · 2014Review
- Article
- Redox control of prion and disease pathogenesis.Antioxidants & redox signaling · 2010Review
- Prion protein and metal interaction: physiological and pathological implications.Current issues in molecular biology · 2010Review
- Hereditary haemochromatosis gene (HFE) H63D mutation shows an association with abnormal sperm motility.Molecular biology reports · 2009Article
- Increased susceptibility to Mycobacterium avium in hemochromatosis protein HFE-deficient mice.Infection and immunity · 2008Article
- Intracellular iron transport and storage: from molecular mechanisms to health implications.Antioxidants & redox signaling · 2008Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The protein defective in hereditary hemochromatosis, called HFE, is similar to MHC class I-type proteins and associates with beta2-microglobulin (beta2M). Its association with beta2M was previously shown to be necessary for its stability, normal intracellular processing, and cell surface expression in transfected COS cells. Here we use stably transfected Chinese hamster ovary cell lines expressing both HFE and beta2M or HFE alone to study the effects of beta2M on the stability and maturation of the HFE protein and on the role of HFE in transferrin receptor 1 (TfR1)-mediated iron uptake. In agreement with prior studies on other cell lines, we found that overexpression of HFE, without overexpressing beta2M, resulted in a decrease in TfR1dependent iron uptake and in lower iron levels in the cells, as evidenced by ferritin and TfR1 levels measured at steady state. However, overexpression of both HFE and beta2M had the reverse effect and resulted in an increase in TfR1-dependent iron uptake and increased iron levels in the cells. The HFE-beta2M complex did not affect the affinity of TfR1 for transferrin or the internalization rate of transferrin-bound TfR1. Instead, HFE-beta2M enhanced the rate of recycling of TfR1 and resulted in an increase in the steady-state level of TfR1 at the cell surface of stably transfected cells. We propose that Chinese hamster ovary cells provide a model to explain the effect of the HFE-beta2M complex in duodenal crypt cells, where the HFE-beta2M complex appears to facilitate the uptake of transferrin-bound iron to sense the level of body iron stores. Impairment of this process in duodenal crypt cells leads them to be iron poor and to signal the differentiating enterocytes to take up iron excessively after they mature into villus cells in the duodenum of hereditary hemochromatosis patients.
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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.