ArticleBiometals : an international journal on the role of metal ions in biology, biochemistry, and medicine2012
Isoform specific regulation of divalent metal (ion) transporter (DMT1) by proteasomal degradation.
Article in Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- DMT1 ubiquitination by Nedd4 protects against ferroptosis after intracerebral hemorrhage.CNS neuroscience & therapeutics · 2024Article
- A neurodegeneration gene, WDR45, links impaired ferritinophagy to iron accumulation.Journal of neurochemistry · 2022Article
- Inflaming the Brain with Iron.Antioxidants (Basel, Switzerland) · 2021Review
- Deferoxamine Counteracts Cisplatin Resistance in A549 Lung Adenocarcinoma Cells by Increasing Vulnerability to Glutamine Deprivation-Induced Cell Death.Frontiers in oncology · 2021Article
- Overdosing on iron: Elevated iron and degenerative brain disorders.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- The S-nitrosylation of parkin attenuated the ubiquitination of divalent metal transporter 1 in MPPScientific reports · 2020Article
- DMT1 Expression and Iron Levels at the Crossroads Between Aging and Neurodegeneration.Frontiers in neuroscience · 2019Review
- A role for divalent metal transporter (DMT1) in mitochondrial uptake of iron and manganese.Scientific reports · 2018Article
- Lower Expression of Ndfip1 Is Associated With Alzheimer Disease Pathogenesis Through Decreasing DMT1 Degradation and Increasing Iron Influx.Frontiers in aging neuroscience · 2018Article
- Protoporphyrin IX regulates peripheral benzodiazepine receptor associated protein 7 (PAP7) and divalent metal transporter 1 (DMT1) in K562 cells.Biochemistry and biophysics reports · 2017Article
- Brain Iron Metabolism Dysfunction in Parkinson's Disease.Molecular neurobiology · 2017Review
- Ferrous Iron Up-regulation in Fibroblasts of Patients with Beta Propeller Protein-Associated Neurodegeneration (BPAN).Frontiers in genetics · 2017Article
- Ototoxicity of Divalent Metals.Neurotoxicity research · 2016Review
- Ndfip2 is a potential regulator of the iron transporter DMT1 in the liver.Scientific reports · 2016Article
- Regulation of the divalent metal ion transporter via membrane budding.Cell discovery · 2016Article
- Cobalt-Induced Ototoxicity in Rat Postnatal Cochlear Organotypic Cultures.Neurotoxicity research · 2015Article
- Changes of ferrous iron and its transporters after intracerebral hemorrhage in rats.International journal of clinical and experimental pathology · 2015Article
- Divalent metal transporter 1 (DMT1) in the brain: implications for a role in iron transport at the blood-brain barrier, and neuronal and glial pathology.Frontiers in molecular neuroscience · 2015Review
- Iron homeostasis in peripheral nervous system, still a black box?Antioxidants & redox signaling · 2014Review
- Iron in neurodegenerative disorders of protein misfolding: a case of prion disorders and Parkinson's disease.Antioxidants & redox signaling · 2014Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Divalent metal ion transporter (DMT1) is the major transporter for iron entrance into mammalian cells and iron exit from endosomes during the transferrin cycle. Four major mRNA isoforms correspond to four protein isoforms, differing at 5'/3' and N-/C-termini, respectively. Isoforms are designated 1A versus 1B reflecting where transcription starts or +iron responsive element (+IRE) versus -IRE reflecting the presence/absence of an IRE in the 3' end of the mRNA. These differences imply regulation at transcriptional and posttranscriptional levels. Many proteins are degraded by a ubiquitination-dependent mechanism. Two different ubiquitin ligases (E3s) appear to be involved in DMT1 ubiquitination: Parkin or neuronal precursor cell-expressed developmentally downregulated 4 (Nedd4) family E3s which often utilize Nedd4 family interacting protein-1 and -2 (Ndfip1 and 2) to ubiquitinate their substrate proteins. Prior data suggest that Parkin ubiquitinates 1B DMT1 but not 1A DMT1 while Nedd4/Ndfips ligate ubiquitin to DMT1 in the duodenum where 1A/+IRE DMT1 predominates. Our assay for whether these systems target DMT1 depends on two HEK293 cell lines that express permanently transfected 1A/+IRE DMT1 or 1B/-IRE DMT1 after induction by doxycycline. Transient transfection with a Parkin construct before induction diminishes 1B/-IRE DMT1 detected by immune-blots but not 1A/+IRE DMT1. Mutant Parkin serves as a control that does not affect DMT1 levels. Thus DMT1 regulation in an isoform specific fashion can occur by ubiquitination and the events involved have implications for DMT1 function and disease processes.
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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.