ArticleProceedings of the National Academy of Sciences of the United States of America2021
Mediator subunit MED1 is required for E2A-PBX1-mediated oncogenic transcription and leukemic cell growth.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- A Brief Review on the Role of the Transcription Factor PBX1 in Hematologic Malignancies.International journal of molecular sciences · 2025Review
- Biomolecular condensates in immune cell fate.Nature reviews. Immunology · 2025Review
- Integrated multi-omics analysis of PBX1 in mouse adult neural stem- and progenitor cells identifies a transcriptional module that functionally links PBX1 to TCF3/4.Nucleic acids research · 2024Article
- Mediator complex subunit 1 promotes oral squamous cell carcinoma progression by activating MMP9 transcription and suppressing CD8Journal of experimental & clinical cancer research : CR · 2024Article
- TAF2, within the TFIID complex, regulates the expression of a subset of protein-coding genes.Cell death discovery · 2024Article
- [Identification of key genes in Wilms tumor based on high-throughput RNA sequencing and their impacts on prognosis and immune responses].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- PBX1: a TALE of two seasons-key roles during development and in cancer.Frontiers in cell and developmental biology · 2024Review
- Comprehensive summary: the role of PBX1 in development and cancers.Frontiers in cell and developmental biology · 2024Review
- Regulation of the RNA polymerase II pre-initiation complex by its associated coactivators.Nature reviews. Genetics · 2023Review
- Recent Advances in Transcription Factors Biomarkers and Targeted Therapies Focusing on Epithelial-Mesenchymal Transition.Cancers · 2023Review
- Biomolecular condensates: Formation mechanisms, biological functions, and therapeutic targets.MedComm · 2023Review
- Spindle function and Wnt pathway inhibition by PBX1 to suppress tumor progression via downregulating DCDC2 in colorectal cancer.Oncogenesis · 2023Article
- Comprehensive overview of the role of PBX1 in mammalian kidneys.Frontiers in molecular biosciences · 2023Review
- NetREX-CF integrates incomplete transcription factor data with gene expression to reconstruct gene regulatory networks.Communications biology · 2022Article
- The Mediator complex as a master regulator of transcription by RNA polymerase II.Nature reviews. Molecular cell biology · 2022Review
- Targeting SPHK1/PBX1 Axis Induced Cell Cycle Arrest in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2022Article
- Liquid-liquid phase separation in tumor biology.Signal transduction and targeted therapy · 2022Review
- Bioinformatics Identification of Candidate Biomarkers in Endomyocardial Biopsy and Peripheral Blood for Cardiac Allograft Rejection.Annals of transplantation · 2022Article
- The role of E2A in ATPR-induced cell differentiation and cycle arrest in acute myeloid leukaemia cells.Journal of cellular and molecular medicine · 2022Article
- USP7 facilitates SMAD3 autoregulation to repress cancer progression in p53-deficient lung cancer.Cell death & disease · 2021Article
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9 authors at 3 institutions in 2 countries.
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Abstract
The chimeric transcription factor E2A-PBX1, containing the N-terminal activation domains of E2A fused to the C-terminal DNA-binding domain of PBX1, results in 5% of pediatric acute lymphoblastic leukemias (ALL). We recently have reported a mechanism for RUNX1-dependent recruitment of E2A-PBX1 to chromatin in pre-B leukemic cells; but the subsequent E2A-PBX1 functions through various coactivators and the general transcriptional machinery remain unclear. The Mediator complex plays a critical role in cell-specific gene activation by serving as a key coactivator for gene-specific transcription factors that facilitates their function through the RNA polymerase II transcriptional machinery, but whether Mediator contributes to aberrant expression of E2A-PBX1 target genes remains largely unexplored. Here we show that Mediator interacts directly with E2A-PBX1 through an interaction of the MED1 subunit with an E2A activation domain. Results of MED1 depletion by CRISPR/Cas9 further indicate that MED1 is specifically required for E2A-PBX1-dependent gene activation and leukemic cell growth. Integrated transcriptome and cistrome analyses identify pre-B cell receptor and cell cycle regulatory genes as direct cotargets of MED1 and E2A-PBX1. Notably, complementary biochemical analyses also demonstrate that recruitment of E2A-PBX1 to a target DNA template involves a direct interaction with DNA-bound RUNX1 that can be further stabilized by EBF1. These findings suggest that E2A-PBX1 interactions with RUNX1 and MED1/Mediator are of functional importance for both gene-specific transcriptional activation and maintenance of E2A-PBX1-driven leukemia. The MED1 dependency for E2A-PBX1-mediated gene activation and leukemogenesis may provide a potential therapeutic opportunity by targeting MED1 in E2A-PBX1
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