ArticleCell death & disease2013
Caspase-3 cleaves hnRNP K in erythroid differentiation.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Caspase-3 regulates RNA splicing and mitochondrial dynamics in microglia during Parkinson's disease.Cell death & disease · 2026Article
- Evolution of botulinum neurotoxin serotype X proteases to induce inflammatory cell death in cancer cells.Nature biotechnology · 2026Article
- Article
- Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis.The Journal of cell biology · 2022Review
- Methylated HNRNPK acts on RPS19 to regulate ALOX15 synthesis in erythropoiesis.Nucleic acids research · 2021Article
- Post-translational Control of RNA-Binding Proteins and Disease-Related Dysregulation.Frontiers in molecular biosciences · 2021Review
- Review
- RNA-Binding Proteins in the Control of LPS-Induced Macrophage Response.Frontiers in genetics · 2019Review
- Non-apoptotic functions of caspases in myeloid cell differentiation.Cell death and differentiation · 2017Review
- Aberrant hnRNP K expression: All roads lead to cancer.Cell cycle (Georgetown, Tex.) · 2016Review
- CDK11 in TREX/THOC Regulates HIV mRNA 3' End Processing.Cell host & microbe · 2015Article
- Cyclin C mediates stress-induced mitochondrial fission and apoptosis.Molecular biology of the cell · 2015Article
- Arginine methylation of hnRNPK negatively modulates apoptosis upon DNA damage through local regulation of phosphorylation.Nucleic acids research · 2014Article
- Translation control of TAK1 mRNA by hnRNP K modulates LPS-induced macrophage activation.RNA (New York, N.Y.) · 2014Article
- Functions of heterogeneous nuclear ribonucleoproteins in stem cell potency and differentiation.BioMed research international · 2013Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Post-transcriptional control of gene expression is crucial for the control of cellular differentiation. Erythroid precursor cells loose their organelles in a timely controlled manner during terminal maturation to functional erythrocytes. Extrusion of the nucleus precedes the release of young reticulocytes into the blood stream. The degradation of mitochondria is initiated by reticulocyte 15-lipoxygenase (r15-LOX) in mature reticulocytes. At that terminal stage the release of r15-LOX mRNA from its translational silenced state induces the synthesis of r15-LOX. Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a key regulator of r15-LOX mRNA translation. HnRNP K that binds to the differentiation control element (DICE) in the 3' untranslated region (UTR) inhibits r15-LOX mRNA translation initiation. During erythroid cell maturation, activation of r15-LOX mRNA translation is mediated by post-translational modifications of hnRNP K and a decrease of the hnRNP K level. To further elucidate its function in the post-transcriptional control of gene expression, we investigated hnRNP K degradation employing an inducible erythroid cell system that recapitulates both nuclear extrusion and the timely controlled degradation of mitochondria, mediated by the activation of r15-LOX synthesis. Interestingly, we detected a specific N-terminal cleavage intermediate of hnRNP K lacking DICE-binding activity that appeared during erythroid differentiation and puromycin-induced apoptosis. Employing mass spectrometry and enzymatic analyses, we identified Caspase-3 as the enzyme that cleaves hnRNP K specifically. In vitro studies revealed that cleavage by Caspase-3 at amino acids (aa) D334-G335 removes the C-terminal hnRNP K homology (KH) domain 3 that confers binding of hnRNP K to the DICE. Our data suggest that the processing of hnRNP K by Caspase-3 provides a save-lock mechanism for its timely release from the r15-LOX mRNA silencing complex and activation of r15-LOX mRNA synthesis in erythroid cell differentiation.
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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.