ArticleMolecular and cellular biology1994
Transformation properties of the E2a-Pbx1 chimeric oncoprotein: fusion with E2a is essential, but the Pbx1 homeodomain is dispensable.
Article in Molecular and cellular biology, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 107 citations in OpenAlex.
- The advances of E2A-PBX1 fusion in B-cell acute lymphoblastic Leukaemia.Annals of hematology · 2024Review
- Mediator subunit MED1 is required for E2A-PBX1-mediated oncogenic transcription and leukemic cell growth.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cell Fate Decisions: The Role of Transcription Factors in Early B-cell Development and Leukemia.Blood cancer discovery · 2020Review
- Article
- Oligomeric self-association contributes to E2A-PBX1-mediated oncogenesis.Scientific reports · 2019Article
- Acute lymphoblastic leukemia of the central nervous system: on the role of PBX1.Haematologica · 2017Article
- Mechanisms of human lymphoid chromosomal translocations.Nature reviews. Cancer · 2016Review
- Comparative genomics reveals multistep pathogenesis of E2A-PBX1 acute lymphoblastic leukemia.The Journal of clinical investigation · 2015Article
- Article
- Fusion of the genes EWSR1 and PBX3 in retroperitoneal leiomyoma with t(9;22)(q33;q12).PloS one · 2015Article
- Functional redundancy between the transcriptional activation domains of E2A is mediated by binding to the KIX domain of CBP/p300.Nucleic acids research · 2014Article
- Differential involvement of E2A-corepressor interactions in distinct leukemogenic pathways.Nucleic acids research · 2014Article
- Genetically engineered mouse models of human B-cell precursor leukemias.Cell cycle (Georgetown, Tex.) · 2014Review
- E proteins in lymphocyte development and lymphoid diseases.Current topics in developmental biology · 2014Review
- Murine models of acute leukemia: important tools in current pediatric leukemia research.Frontiers in oncology · 2014Review
- Article
- Detection of E2A-PBX1 fusion transcripts in human non-small-cell lung cancer.Journal of experimental & clinical cancer research : CR · 2013Article
- GCN5 acetylates and regulates the stability of the oncoprotein E2A-PBX1 in acute lymphoblastic leukemia.Leukemia · 2013Article
- Histone H3 lysine 79 methyltransferase Dot1 is required for immortalization by MLL oncogenes.Cancer research · 2010Article
- Mechanisms of chromosomal rearrangement in the human genome.BMC genomics · 2010Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The t(1;19) chromosomal translocation in acute lymphoblastic leukemias creates chimeric E2a-Pbx1 oncoproteins that can act as DNA-binding activators of transcription. A structural analysis of the functional domains of E2a-Pbx1 showed that portions of both E2a and Pbx1 were essential for transformation of NIH 3T3 cells and transcriptional activation of synthetic reporter genes containing PBX1 consensus binding sites. Hyperexpression of wild-type or experimentally truncated Pbx1 proteins was insufficient for transformation, consistent with their inability to activate transcription. When fused with E2a, the Pbx-related proteins Pbx2 and Pbx3 were also transformation competent, demonstrating that all known members of this highly similar subfamily of homeodomain proteins have latent oncogenic potential. The oncogenic contributions of E2a to the chimeras were localized to transactivation motifs AD1 and AD2, as their mutation significantly impaired transformation. Either the homeodomain or Pbx1 amino acids flanking this region could mediate transformation when fused to E2a. However, the homeodomain was not essential for transformation, since a mutant E2a-Pbx1 protein (E2a-Pbx delta HD) lacking the homeodomain efficiently transformed fibroblasts and induced malignant lymphomas in transgenic mice. Thus, transformation mediated by the chimeric oncoprotein E2a-Pbx1 is absolutely dependent on motifs acquired from E2a but the Pbx1 homeodomain is optional. The latter finding suggests that E2a-Pbx1 may interact with cellular proteins that assist or mediate alterations in gene expression responsible for oncogenesis even in the absence of homeodomain-DNA interactions.
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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.