ArticleMolecular and cellular biology2002
MLL-AFX requires the transcriptional effector domains of AFX to transform myeloid progenitors and transdominantly interfere with forkhead protein function.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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.
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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
40 citing papers in PubMed, 103 citations in OpenAlex.
- Recognition of two hydrophobic pockets in the KIX domain of CBP by FOXO4 transactivation domain.Communications biology · 2025Article
- KMT2A-rearranged leukemia: from mechanism to drug development.Experimental hematology · 2025Review
- Role of the MOZ/MLL-mediated transcriptional activation system for self-renewal in normal hematopoiesis and leukemogenesis.The FEBS journal · 2022Review
- Leukemogenesis via aberrant self-renewal by the MLL/AEP-mediated transcriptional activation system.Cancer science · 2021Review
- Molecular Dynamics Simulations of Human FOXO3 Reveal Intrinsically Disordered Regions Spread Spatially by Intramolecular Electrostatic Repulsion.Biomolecules · 2021Article
- Review
- Review
- Forkhead Domains of FOXO Transcription Factors Differ in both Overall Conformation and Dynamics.Cells · 2019Article
- Transcription factors FOXO in the regulation of homeostatic hematopoiesis.Current opinion in hematology · 2018Review
- FOXO in Neural Cells and Diseases of the Nervous System.Current topics in developmental biology · 2018Review
- Structural characterization of interactions between transactivation domain 1 of the p65 subunit of NF-κB and transcription regulatory factors.Nucleic acids research · 2017Article
- miR-150 exerts antileukemia activity in vitro and in vivo through regulating genes in multiple pathways.Cell death & disease · 2016Article
- FOXO transcription factors in cancer development and therapy.Cellular and molecular life sciences : CMLS · 2016Review
- The epigenetic regulators CBP and p300 facilitate leukemogenesis and represent therapeutic targets in acute myeloid leukemia.Oncogene · 2016Article
- Redox regulation of FoxO transcription factors.Redox biology · 2015Review
- Critical role of retinoid/rexinoid signaling in mediating transformation and therapeutic response of NUP98-RARG leukemia.Leukemia · 2015Article
- Molecular mechanisms of MLL-associated leukemia.International journal of hematology · 2015Review
- Forkhead followed by disordered tail: The intrinsically disordered regions of FOXO3a.Intrinsically disordered proteins · 2015Review
- The PAX3-FOXO1 fusion protein present in rhabdomyosarcoma interferes with normal FOXO activity and the TGF-β pathway.PloS one · 2015Article
- Transcriptional/epigenetic regulator CBP/p300 in tumorigenesis: structural and functional versatility in target recognition.Cellular and molecular life sciences : CMLS · 2013Review
Corrections and comments
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2 authors at 1 institution in 1 country.
Funding
Abstract
MLL-AFX is a fusion gene created by t(X;11) chromosomal translocations in a subset of acute leukemias of either myeloid or lymphoid derivation. It codes for a chimeric protein consisting of MLL fused to AFX, a forkhead transcription factor that normally regulates genes involved in apoptosis and cell cycle progression. We demonstrate here that forced expression of MLL-AFX enhances the self-renewal of hematopoietic progenitors in vitro and induces acute myeloid leukemias after long latencies in syngeneic recipient mice. MLL-AFX interacts with the transcriptional coactivator CBP, which is also a fusion partner for MLL in human leukemias. A potent minimal transactivation domain (CR3) at the C terminus of AFX mediates interactions with the KIX domain of CBP and is necessary for transformation of myeloid progenitors by MLL-AFX. However, CR3 alone is not sufficient, suggesting that simple acquisition of a transactivation domain per se does not activate the oncogenic potential of MLL. Rather, two conserved transcriptional effector domains (CR2 and CR3) of AFX are required for full oncogenicity of MLL-AFX and also endow it with the potential to competitively interfere with transcription and apoptosis mediated by wild-type forkhead proteins. Furthermore, a dominant-negative mutant of AFX containing CR2 and CR3 enhances the growth of myeloid progenitors in vitro, although considerably less effectively than does MLL-AFX. Taken together, these data suggest that recruitment of transcriptional cofactors utilized by forkhead proteins is a critical requirement for oncogenic action of MLL-AFX, which may impact both MLL- and forkhead-dependent transcriptional pathways.
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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 Socratic graph.