ArticleBlood2013
Improved ex vivo expansion of adult hematopoietic stem cells by overcoming CUL4-mediated degradation of HOXB4.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Prolonging somatic cell proliferation through constitutive hox gene expression in C. elegans.Nature communications · 2023Article
- HOXA3 accelerates wound healing in diabetic and aged non-diabetic mammals.Scientific reports · 2023Article
- Current approaches and potential challenges in the delivery of gene editing cargos into hematopoietic stem and progenitor cells.Frontiers in genome editing · 2023Review
- G3BP1 inhibits Cul3Nature communications · 2021Article
- The Future of Gene Therapy for Transfusion-Dependent Beta-Thalassemia: The Power of the Lentiviral Vector for Genetically Modified Hematopoietic Stem Cells.Frontiers in pharmacology · 2021Review
- CUL4 E3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinoma.Cancer biology & medicine · 2020Article
- The emerging role for Cullin 4 family of E3 ligases in tumorigenesis.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Repopulating hematopoietic stem cells from steady-state blood before and afterHaematologica · 2018Article
- The Role of N-Acetylcysteine Supplementation on the Oxidative Stress Levels, Genotoxicity and Lineage Commitment Potential ofSultan Qaboos University medical journal · 2018Article
- Article
- Hit-and-run programming of therapeutic cytoreagents using mRNA nanocarriers.Nature communications · 2017Article
- Recombinant TAT-BMI-1 fusion protein induces ex vivo expansion of human umbilical cord blood-derived hematopoietic stem cells.Oncotarget · 2017Article
- Dysregulation of CUL4A and CUL4B Ubiquitin Ligases in Lung Cancer.The Journal of biological chemistry · 2017Article
- Enhancing the efficacy of engraftment of cord blood for hematopoietic cell transplantation.Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis · 2016Review
- Cell Autonomous and Nonautonomous Function of CUL4B in Mouse Spermatogenesis.The Journal of biological chemistry · 2016Article
- Article
- Distinct and overlapping functions of the cullin E3 ligase scaffolding proteins CUL4A and CUL4B.Gene · 2015Review
- CDK4/6 Inhibitor PD 0332991 Sensitizes Acute Myeloid Leukemia to Cytarabine-Mediated Cytotoxicity.Cancer research · 2015Article
- Article
- Comparison of stem/progenitor cell number and transcriptomic profile in the mammary tissue of dairy and beef breed heifers.Journal of applied genetics · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Direct transduction of the homeobox (HOX) protein HOXB4 promotes the proliferation of hematopoietic stem cells (HSCs) without induction of leukemogenesis, but requires frequent administration to overcome its short protein half-life (∼1 hour). We demonstrate here that HOXB4 protein levels are post-translationally regulated by the CUL4 ubiquitin ligase, and define the degradation signal sequence (degron) of HOXB4 required for CUL4-mediated destruction. Additional HOX paralogs share the conserved degron in the homeodomain and are also subject to CUL4-mediated degradation, indicating that CUL4 likely controls the stability of all HOX proteins. Moreover, we engineered a degradation-resistant HOXB4 that conferred a growth advantage over wild-type HOXB4 in myeloid progenitor cells. Direct transduction of recombinant degradation-resistant HOXB4 protein to human adult HSCs significantly enhanced their maintenance in a more primitive state both in vitro and in transplanted NOD/SCID/IL2R-γ(null) mice compared with transduction with wild-type HOXB4 protein. Our studies demonstrate the feasibility of engineering a stable HOXB4 variant to overcome a major technical hurdle in the ex vivo expansion of adult HSCs and early progenitors for human therapeutic use.
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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.