ArticleScientific reports2017
Asxl1 deficiency in embryonic fibroblasts leads to cellular senescence via impairment of the AKT-E2F pathway and Ezh2 inactivation.
Article in Scientific reports, 2017. 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, 26 citations in OpenAlex.
- A Zebrafish Seizure Model of cblX Syndrome Reveals a Dose-Dependent Response to mTor Inhibition.Journal of developmental biology · 2025Article
- Asxl1 loss in mice leads to microcephaly by regulating neural stem cell survival.Animal cells and systems · 2025Article
- Exploring the therapeutic mechanisms of Coptidis Rhizoma in gastric precancerous lesions: a network pharmacology approach.Discover oncology · 2024Article
- Additional Sex Combs-like Family Associated with Epigenetic Regulation.International journal of molecular sciences · 2024Review
- Article
- Epigenetic roles in clonal hematopoiesis and aging kidney-related chronic kidney disease.Frontiers in cell and developmental biology · 2023Review
- CHIP-associated mutant ASXL1 in blood cells promotes solid tumor progression.Cancer science · 2022Article
- Hcfc1a regulates neural precursor proliferation and asxl1 expression in the developing brain.BMC neuroscience · 2020Article
- Crosstalk between histone modification and DNA methylation orchestrates the epigenetic regulation of the costimulatory factors, Tim‑3 and galectin‑9, in cervical cancer.Oncology reports · 2019Article
- RUNX1 mutations promote leukemogenesis of myeloid malignancies in ASXL1-mutated leukemia.Journal of hematology & oncology · 2019Article
- Aberrant histone modifications induced by mutant ASXL1 in myeloid neoplasms.International journal of hematology · 2019Review
- The role of ASXL1 in hematopoiesis and myeloid malignancies.Cellular and molecular life sciences : CMLS · 2019Review
- Article
- Role ofOncotarget · 2018Article
- Asxl1 exerts an antiproliferative effect on mouse lung maturation via epigenetic repression of the E2f1-Nmyc axis.Cell death & disease · 2018Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although ASXL1 mutations are frequently found in human diseases, including myeloid leukemia, the cell proliferation-associated function of ASXL1 is largely unknown. Here, we explored the molecular mechanism underlying the growth defect found in Asxl1-deficient mouse embryonic fibroblasts (MEFs). We found that Asxl1, through amino acids 371 to 655, interacts with the kinase domain of AKT1. In Asxl1-null MEFs, IGF-1 was unable to induce AKT1 phosphorylation and activation; p27Kip1, which forms a ternary complex with ASXL1 and AKT1, therefore remained unphosphorylated. Hypophosphorylated p27Kip1 is able to enter the nucleus, where it prevents the phosphorylation of Rb; this ultimately leads to the down-regulation of E2F target genes as confirmed by microarray analysis. We also found that senescence-associated (SA) genes were upregulated and that SA β-gal staining was increased in Asxl1
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