ReviewCurrent opinion in hematology2014
Translational control by heme-regulated eIF2α kinase during erythropoiesis.
Review in Current opinion in hematology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 83 citations in OpenAlex.
- Regulation of Translation of ATF4 mRNA: A Focus on Translation Initiation Factors and RNA-Binding Proteins.Cells · 2026Review
- HRI protein kinase in cytoplasmic heme sensing and mitochondrial stress response: Relevance to hematological and mitochondrial diseases.The Journal of biological chemistry · 2025Review
- Integrated Stress Response Potentiates Ponatinib-Induced Cardiotoxicity.Circulation research · 2024Article
- The integrated stress response protects against ER stress but is not required for altered translation and lifespan from dietary restriction inFrontiers in cell and developmental biology · 2023Article
- Targeting the EIF2AK1 Signaling Pathway Rescues Red Blood Cell Production in SF3B1-Mutant Myelodysplastic Syndromes With Ringed Sideroblasts.Blood cancer discovery · 2022Article
- Redox Balance in β-Thalassemia and Sickle Cell Disease: A Love and Hate Relationship.Antioxidants (Basel, Switzerland) · 2022Review
- Mechanisms tailoring the expression of heat shock proteins to proteostasis challenges.The Journal of biological chemistry · 2022Review
- Targeting elevated heme levels to treat a mouse model for Diamond-Blackfan Anemia.Experimental hematology · 2022Article
- Targeting the integrated stress response in ophthalmology.Current eye research · 2021Review
- Article
- Mitochondria Biogenesis Modulates Iron-Sulfur Cluster Synthesis to Increase Cellular Iron Uptake.DNA and cell biology · 2020Article
- The integrated stress response: From mechanism to disease.Science (New York, N.Y.) · 2020Review
- Enasidenib drives human erythroid differentiation independently of isocitrate dehydrogenase 2.The Journal of clinical investigation · 2020Article
- Requirement of activating transcription factor 5 for murine fetal liver erythropoiesis.British journal of haematology · 2020Article
- TFII-I/Gtf2i and Erythro-Megakaryopoiesis.Frontiers in physiology · 2020Article
- Normal Iron Homeostasis Requires the Transporter SLC48A1 for Efficient Heme-Iron Recycling in Mammals.Frontiers in genome editing · 2020Article
- Review
- δ-Aminolevulinate induces fetal hemoglobin expression by enhancing cellular heme biosynthesis.Experimental biology and medicine (Maywood, N.J.) · 2019Article
- BOK promotes erythropoiesis in a mouse model of myelodysplastic syndrome.Annals of hematology · 2019Article
- Dimeric ferrochelatase bridges ABCB7 and ABCB10 homodimers in an architecturally defined molecular complex required for heme biosynthesis.Haematologica · 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
1 author at 1 institution in 1 country.
Funding
Abstract
purpose of reviewThis review will provide an overview of the translational regulation of globin mRNAs and integrated stress response (ISR) during erythropoiesis by heme-regulated eIF2α kinase (HRI). HRI is an intracellular heme sensor that coordinates heme and globin synthesis in erythropoiesis by inhibiting protein synthesis of globins and heme biosynthetic enzymes during heme deficiency. RECENT
findingsIt has been demonstrated recently that HRI also activates the eIF2αP-activating transcription factor 4 (ATF4) ISR in primary erythroid precursors to combat oxidative stress. During chronic iron/heme deficiency in vivo, this HRI-eIF2αP-ATF4 signaling is necessary both to reduce oxidative stress and to promote erythroid differentiation. Augmenting eIF2αP signaling by the small molecule salubrinal, which inhibits dephosphorylation of eIF2αP, reduces excess α-globin synthesis and enhances translation of ATF4 mRNA in mouse β-thalassemic erythroid precursors. Intriguingly, salubrinal treatment of differentiating human CD34⁺ cells in culture increases fetal hemoglobin production with a concomitant decrease of adult hemoglobin by a posttranscriptional mechanism. SUMMARY: HRI-eIF2αP-ATF4 stress signaling is important not only to inhibit excess globin synthesis during erythropoiesis, but is also critical for adaptation to oxidative stress and for enhancing effective erythropoiesis. Modulation of this signaling pathway with small chemicals may provide a novel therapy for hemoglobinopathy.
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.