ArticleProceedings of the National Academy of Sciences of the United States of America2011
Function of leukemogenic mixed lineage leukemia 1 (MLL) fusion proteins through distinct partner protein complexes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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
113 citing papers in PubMed, 167 citations in OpenAlex.
- SEC Mediates mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Acetylation-independent mechanism for binding of ENL to intrinsically disordered regions in TAF2/6 and SNF5.Nucleic acids research · 2026Article
- Therapeutic Advances in Adult B-cell Acute Lymphoblastic Leukemia with KMT2A Rearrangements.Annals of hematology · 2026Review
- Article
- The Arabidopsis thaliana AtCARP9 is a novel ELL ortholog and associates with AtEAF proteins.Planta · 2026Article
- Menin Inhibition in Acute Myeloid Leukemia: Rewiring Leukemic Transcriptional Networks.International journal of molecular sciences · 2026Review
- Dynamic partitioning of a critical elongation factor between LEC and SEC regulates cellular snRNA and proliferation-related mRNA transcription.Nature communications · 2026Article
- Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- A multivalent engagement of ENL with MOZ.Nature structural & molecular biology · 2025Article
- Expression of ENL YEATS domain tumor mutations in nephrogenic or stromal lineage impairs kidney development.Nature communications · 2025Article
- Histone methyltransferase KMT2A: Developmental regulation to oncogenic transformation.The Journal of biological chemistry · 2024Review
- A potent and selective ENL degrader suppresses oncogenic gene expression and leukemia progression.Science advances · 2024Article
- Condensate-Promoting ENL Mutation Drives Tumorigenesis In Vivo Through Dynamic Regulation of Histone Modifications and Gene Expression.Cancer discovery · 2024Article
- Post-translational modification-dependent oligomerization switch in regulation of global transcription and DNA damage repair during genotoxic stress.Nature communications · 2024Article
- Leveraging a Phage-Encoded Noncanonical Amino Acid: A Novel Pathway to Potent and Selective Epigenetic Reader Protein Inhibitors.ACS central science · 2024Article
- The Biological Significance of AFF4: Promoting Transcription Elongation, Osteogenic Differentiation and Tumor Progression.Combinatorial chemistry & high throughput screening · 2024Review
- The human leukemic oncogene MLL-AF4 promotes hyperplastic growth of hematopoietic tissues iniScience · 2023Article
- MLL-AF4 cooperates with PAF1 and FACT to drive high-density enhancer interactions in leukemia.Nature communications · 2023Article
- Degradation of CDK9 by Ubiquitin E3 Ligase STUB1 Regulates P-TEFb Level and Its Functions for Global Target Gene Expression within Mammalian Cells.Molecular and cellular biology · 2023Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
A number of acute leukemias arise from fusion of the mixed lineage leukemia 1 protein (MLL) N terminus to a variety of fusion partners that have been reported to reside in one or more poorly defined complexes linked to transcription elongation through interactions with the histone H3-K79 methyltransferase DOT1 and positive transcription elongation factor b (P-TEFb). Here we first identify natural complexes (purified through fusion partners AF9, AF4, and ELL) with overlapping components, different elongation activities, and different cofactor associations that suggest dynamic interactions. Then, through reconstitution of defined, functionally active minimal complexes, we identify stable subcomplexes that, through newly defined protein-protein interactions, form distinct higher order complexes. These definitive analyses show, for example, that (i) through direct interactions with AF9 and cyclinT1, family members AF4 and AFF4 independently mediate association of P-TEFb with AF9, (ii) P-TEFb, through direct interactions, provides the link for association of ELL and ELL-associated factors 1 and 2 (EAF1 and EAF2) with AF4, and (iii) in the absence of other factors, DOT1 forms a stable complex with AF9 and does not interact with AF9•AF4•P-TEFb complexes. Finally, we show the importance of defined higher order complex formation in MLL-AF9-mediated transcriptional up-regulation and cell immortalization potential in vivo. Thus, our study provides direct mechanistic insight into the role of fusion partners in MLL fusion-mediated leukemogenesis.
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.