ArticleBlood2014
Thrombopoietin promotes NHEJ DNA repair in hematopoietic stem cells through specific activation of Erk and NF-κB pathways and their target, IEX-1.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 87 citations in OpenAlex.
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- Interleukin-33 (IL-33) promotes DNA damage-resistance in lung cancer.Cell death & disease · 2025Article
- IER3: exploring its dual function as an oncogene and tumor suppressor.Cancer gene therapy · 2025Article
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- A review on the functional characteristics of the c-Myeloproliferative Leukaemia (c-MPL) gene and its isoforms.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Comprehensive analysis of bulk, single-cell RNA sequencing, and spatial transcriptomics revealed IER3 for predicting malignant progression and immunotherapy efficacy in glioma.Cancer cell international · 2024Article
- Thrombopoietin mimetic stimulates bone marrow vascular and stromal niches to mitigate acute radiation syndrome.Stem cell research & therapy · 2024Article
- Thrombopoietin mimetic stimulates bone marrow vascular and stromal niches to mitigate acute radiation syndrome.Research square · 2024Article
- Influences on the Hematopoietic Stem Cell Niche.SciBase hematology & blood disorders · 2024Article
- PEGylated thrombopoietin mimetic, JNJ‑26366821 a novel prophylactic radiation countermeasure for acute radiation injury.Scientific reports · 2023Article
- Thrombopoietin receptor agonist antibody for treating chemotherapy-induced thrombocytopenia.BMC cancer · 2023Article
- rhTPO Ameliorates Radiation-Induced Long-Term Hematopoietic Stem Cell Injury in Mice.Molecules (Basel, Switzerland) · 2023Article
- NF-κB signaling controls H3K9me3 levels at intronic LINE-1 and hematopoietic stem cell genes in cis.The Journal of experimental medicine · 2022Article
- Involvement of classic and alternative non-homologous end joining pathways in hematologic malignancies: targeting strategies for treatment.Experimental hematology & oncology · 2021Review
- Activation of G protein coupled estrogen receptor prevents chemotherapy-induced intestinal mucositis by inhibiting the DNA damage in crypt cell in an extracellular signal-regulated kinase 1- and 2- dependent manner.Cell death & disease · 2021Article
- Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation.eLife · 2021Article
- Adventitial delivery of nanoparticles encapsulated with 1α, 25-dihydroxyvitamin DScientific reports · 2021Article
- MicroRNA-21 maintains hematopoietic stem cell homeostasis through sustaining the NF-κB signaling pathway in mice.Haematologica · 2021Article
- A Review of Romiplostim Mechanism of Action and Clinical Applicability.Drug design, development and therapy · 2021Review
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Loss of hematopoietic stem cell (HSC) function and increased risk of developing hematopoietic malignancies are severe and concerning complications of anticancer radiotherapy and chemotherapy. We have previously shown that thrombopoietin (TPO), a critical HSC regulator, ensures HSC chromosomal integrity and function in response to γ-irradiation by regulating their DNA-damage response. TPO directly affects the double-strand break (DSB) repair machinery through increased DNA-protein kinase (DNA-PK) phosphorylation and nonhomologous end-joining (NHEJ) repair efficiency and fidelity. This effect is not shared by other HSC growth factors, suggesting that TPO triggers a specific signal in HSCs facilitating DNA-PK activation upon DNA damage. The discovery of these unique signaling pathways will provide a means of enhancing TPO-desirable effects on HSCs and improving the safety of anticancer DNA agents. We show here that TPO specifically triggers Erk and nuclear factor κB (NF-κB) pathways in mouse hematopoietic stem and progenitor cells (HSPCs). Both of these pathways are required for a TPO-mediated increase in DSB repair. They cooperate to induce and activate the early stress-response gene, Iex-1 (ier3), upon DNA damage. Iex-1 forms a complex with pERK and the catalytic subunit of DNA-PK, which is necessary and sufficient to promote TPO-increased DNA-PK activation and NHEJ DSB repair in both mouse and human HSPCs.
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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.