ArticleNature medicine2012
Interactions among HCLS1, HAX1 and LEF-1 proteins are essential for G-CSF-triggered granulopoiesis.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
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- HAX1 inhibits apoptosis and promotes maturation of neutrophils.Cell communication and signaling : CCS · 2025Article
- Flavopiridol restores granulopoiesis in experimental models of severe congenital neutropenia.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Identification of key genes and diagnostic biomarkers for peripheral atherosclerosis: A multi-omics approach.Medicine · 2025Article
- A new severe congenital neutropenia syndrome associated with autosomal recessive COPZ1 mutations.Blood · 2025Article
- A strategy to design protein-based antagonists against type I cytokine receptors.PLoS biology · 2024Article
- LYP regulates SLP76 and other adaptor proteins in T cells.Biological research · 2024Article
- Emerging roles of MITF as a crucial regulator of immunity.Experimental & molecular medicine · 2024Review
- High intratumoral plasma cells content in primary prostate cancer defines a subset of tumors with potential susceptibility to immune-based treatments.Prostate cancer and prostatic diseases · 2023Article
- Novel Insights into the Role of Kras in Myeloid Differentiation: Engaging with Wnt/β-Catenin Signaling.Cells · 2023Review
- Extensive Adaptive Variation in Gene Expression within and between Closely Related Horseshoe Bats (Chiroptera,Animals : an open access journal from MDPI · 2022Article
- Extracellular vesicles rich in HAX1 promote angiogenesis by modulating ITGB6 translation.Journal of extracellular vesicles · 2022Article
- A review of granulocyte colony-stimulating factor receptor signaling and regulation with implications for cancer.Frontiers in oncology · 2022Review
- CD147 deficiency is associated with impairedsperm motility/acrosome reaction and offersa therapeutic target for asthenozoospermia.Molecular therapy. Nucleic acids · 2021Article
- A zebrafish model for HAX1-associated congenital neutropenia.Haematologica · 2021Article
- Analysis for interaction between interleukin-35 genes polymorphisms and risk factors on susceptibility to coronary heart disease in the Chinese Han population.BMC cardiovascular disorders · 2021Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
We found that hematopoietic cell-specific Lyn substrate 1 (HCLS1 or HS1) is highly expressed in human myeloid cells and that stimulation with granulocyte colony-stimulating factor (G-CSF) leads to HCLS1 phosphorylation. HCLS1 binds the transcription factor lymphoid-enhancer binding factor 1 (LEF-1), transporting LEF-1 into the nucleus upon G-CSF stimulation and inducing LEF-1 autoregulation. In patients with severe congenital neutropenia, inherited mutations in the gene encoding HCLS1-associated protein X-1 (HAX1) lead to profound defects in G-CSF-triggered phosphorylation of HCLS1 and subsequently to reduced autoregulation and expression of LEF-1. Consistent with these results, HCLS1-deficient mice are neutropenic. In bone marrow biopsies of the majority of tested patients with acute myeloid leukemia, HCLS1 protein expression is substantially elevated, associated with high levels of G-CSF synthesis and, in some individuals, a four-residue insertion in a proline-rich region of HCLS1 protein known to accelerate intracellular signaling. These data demonstrate the importance of HCLS1 in myelopoiesis in vitro and in vivo.
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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.