ArticleJournal of cell science2011
Proteolytically cleaved MLL subunits are susceptible to distinct degradation pathways.
Article in Journal of cell science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Molecular mechanisms of the MLL4 complex in H3K4 methylation and p53-dependent transcription activation.Molecular cell · 2026Article
- KMT2A-rearranged leukemia: from mechanism to drug development.Experimental hematology · 2025Review
- Unveiling the Molecular Landscape of Pancreatic Ductal Adenocarcinoma: Insights into the Role of the COMPASS-like Complex.International journal of molecular sciences · 2024Review
- Cla4 phosphorylates histone methyltransferase Set1 to prevent its degradation by the APC/CScience advances · 2023Article
- Non-histone binding functions of PHD fingers.Trends in biochemical sciences · 2023Review
- Missense variants causing Wiedemann-Steiner syndrome preferentially occur in the KMT2A-CXXC domain and are accurately classified using AlphaFold2.PLoS genetics · 2022Article
- Histone methylation in pancreatic cancer and its clinical implications.World journal of gastroenterology · 2021Review
- Structure, function and inhibition of critical protein-protein interactions involving mixed lineage leukemia 1 and its fusion oncoproteins.Journal of hematology & oncology · 2021Review
- Regulation of MLL/COMPASS stability through its proteolytic cleavage by taspase1 as a possible approach for clinical therapy of leukemia.Genes & development · 2019Article
- MLL is required for miRNA-mediated translational repression.Cell discovery · 2019Article
- Novel sub-cellular localizations and intra-molecular interactions may define new functions of Mixed Lineage Leukemia protein.Cell cycle (Georgetown, Tex.) · 2018Article
- Article
- MLL-Rearranged Leukemias-An Update on Science and Clinical Approaches.Frontiers in pediatrics · 2017Review
- TBP loading by AF4 through SL1 is the major rate-limiting step in MLL fusion-dependent transcription.Cell cycle (Georgetown, Tex.) · 2016Article
- AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription.Nature communications · 2015Article
- Molecular mechanisms of MLL-associated leukemia.International journal of hematology · 2015Review
- Taspase1 cleaves MLL1 to activate cyclin E for HER2/neu breast tumorigenesis.Cell research · 2014Article
- A SET-domain-independent role of WRAD complex in cell-cycle regulatory function of mixed lineage leukemia.Nucleic acids research · 2014Article
- Diverse functions of PHD fingers of the MLL/KMT2 subfamily.Biochimica et biophysica acta · 2014Review
- An MLL-dependent network sustains hematopoiesis.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The mixed lineage leukemia (MLL) proto-oncogenic protein is a histone-lysine N-methyltransferase that is produced by proteolytic cleavage and self-association of the respective functionally distinct subunits (MLL(N) and MLL(C)) to form a holocomplex involved in epigenetic transcriptional regulation. On the basis of studies in Drosophila it has been suggested that the separated subunits might also have distinct functions. In this study, we used a genetically engineered mouse line that lacked MLL(C) to show that the MLL(N)-MLL(C) holocomplex is responsible for MLL functions in various developmental processes. The stability of MLL(N) is dependent on its intramolecular interaction with MLL(C), which is mediated through the first and fourth plant homeodomain (PHD) fingers (PHD1 and PHD4) and the phenylalanine/tyrosine-rich (FYRN) domain of MLL(N). Free MLL(N) is destroyed by a mechanism that targets the FYRN domain, whereas free MLL(C) is exported to the cytoplasm and degraded by the proteasome. PHD1 is encoded by an alternatively spliced exon that is occasionally deleted in T-cell leukemia, and its absence produces an MLL mutant protein that is deficient for holocomplex formation. Therefore, this should be a loss-of-function mutant allele, suggesting that the known tumor suppression role of MLL may also apply to the T-cell lineage. Our data demonstrate that the dissociated MLL subunits are subjected to distinct degradation pathways and thus not likely to have separate functions unless the degradation mechanisms are inhibited.
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Registered trials
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