ArticleProtein & cell2021
Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network.
Article in Protein & cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Prognostic value of ASXL1 mutations in patients with primary myelofibrosis and its relationship with clinical features: a meta-analysis.Annals of hematology · 2021Pooled it
- AKT Phosphorylation of FOXK2 at Ser398 Impacts Breast Cancer Cell Growth and Viability.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- pCancer and FOXK2 (Forkhead Box K2): Oncogenic and Tumor-Suppressive Roles of FOXK2 in Cancer.Biochemical genetics · 2026Review
- BAP1 loss impairs IFN-γ signaling and enhances NK cell-mediated cytotoxicity in myeloid leukemia.Cancer immunology, immunotherapy : CII · 2026Article
- CDK6/4 inactivates BAP1 deubiquitinase destabilizing VHL to promote metastatic colonization in liver.Molecular cancer · 2026Article
- The Disordered Region of ASXL1 Acts as an Auto-Regulator Through Condensation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Unleashed condensation by recurrent mutations of an epigenetic regulator promotes cancer.bioRxiv : the preprint server for biology · 2026Article
- Integrating multiple key molecules in uveal melanoma to uncover metastatic and immune microenvironment-related gene signatures.International journal of ophthalmology · 2026Article
- ASXL1 mutation-related clonal hematopoiesis and age-related diseases: clinical evidence and molecular insights.International journal of hematology · 2025Review
- UFMylation maintains tumor suppressor pVHL stability by activating the deubiquitinase BAP1.Science advances · 2025Article
- LN-439A, a novel BAP1 inhibitor, suppresses the growth of basal-like breast cancer by degrading KLF5.Acta pharmacologica Sinica · 2025Article
- A mutant ASXL1-BAP1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- BAP1 complexes with YY1 and RBBP7 and its downstream targets in ccRCC cells.Open life sciences · 2025Article
- A cofactor-induced repressive type of transcription factor condensation can be induced by synthetic peptides to suppress tumorigenesis.The EMBO journal · 2024Article
- Additional Sex Combs-like Family Associated with Epigenetic Regulation.International journal of molecular sciences · 2024Review
- Emerging roles of FOXK2 in cancers and metabolic disorders.Frontiers in oncology · 2024Review
- Article
- A multimorphic mutation in IRF4 causes human autosomal dominant combined immunodeficiency.Science immunology · 2023Article
- FOXK2 transcription factor and its roles in tumorigenesis (Review).Oncology letters · 2022Review
- Combination of ruxolitinib with ABT-737 exhibits synergistic effects in cells carrying concurrent JAK2Investigational new drugs · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region, resulting in the production of C-terminally truncated mutant ASXL1 proteins. How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogenesis are unclear. Here, we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes. We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells, and lose the ability to interact with FOXK1/K2. Specific deletion of the mutant allele eliminates the expression of C-terminally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1, thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes, particularly those involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling pathways. In addition to FOXK1/K2, we also identify other DNA-binding transcription regulators including transcription factors (TFs) which interact with wild-type ASXL1, but not C-terminally truncated mutant. Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth.
Indexed as
Identifiers
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.