ArticleClinical epigenetics2015
Somatic cancer mutations in the MLL3-SET domain alter the catalytic properties of the enzyme.
Article in Clinical epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- An Updated Review on the Significance of DNA and Protein Methyltransferases and De-methylases in Human Diseases: From Molecular Mechanism to Novel Therapeutic Approaches.Current medicinal chemistry · 2024Review
- A CpG island-encoded mechanism protects genes from premature transcription termination.Nature communications · 2023Article
- Clustered PHD domains in KMT2/MLL proteins are attracted by H3K4me3 and H3 acetylation-rich active promoters and enhancers.Cellular and molecular life sciences : CMLS · 2023Article
- Unraveling the Role of the Tyrosine Tetrad from the Binding Site of the Epigenetic Writer MLL3 in the Catalytic Mechanism and Methylation Multiplicity.International journal of molecular sciences · 2022Article
- NGS Analysis Confirms CommonInternational journal of molecular sciences · 2021Article
- Review
- SET1/MLL family of proteins: functions beyond histone methylation.Epigenetics · 2021Review
- Gain-of-Function Genetic Alterations of G9a Drive Oncogenesis.Cancer discovery · 2020Article
- H2B ubiquitylation enhances H3K4 methylation activities of human KMT2 family complexes.Nucleic acids research · 2020Article
- Restoration of KMT2C/MLL3 in human colorectal cancer cells reinforces genome-wide H3K4me1 profiles and influences cell growth and gene expression.Clinical epigenetics · 2020Article
- Racial Disparities in Triple Negative Breast Cancer: A Review of the Role of Biologic and Non-biologic Factors.Frontiers in public health · 2020Review
- COMPASS Ascending: Emerging clues regarding the roles of MLL3/KMT2C and MLL2/KMT2D proteins in cancer.Cancer letters · 2019Review
- Effects of somatic alterations at pathway level are more mechanism-explanatory and clinically applicable to quantity of liver metastases of colorectal cancer.Cancer medicine · 2019Article
- Events of alternative splicing in head and neck cancer via RNA sequencing - an update.BMC genomics · 2019Article
- EZH2-, CHD4-, and IDH-linked epigenetic perturbation and its association with survival in glioma patients.Journal of molecular cell biology · 2017Article
- The Histone Methyltransferase Mixed Lineage Leukemia (MLL) 3 May Play a Potential Role on Clinical Dilated Cardiomyopathy.Molecular medicine (Cambridge, Mass.) · 2017Article
- Somatic cancer mutations in the MLL1 histone methyltransferase modulate its enzymatic activity and dependence on the WDR5/RBBP5/ASH2L complex.Molecular oncology · 2017Article
- Targeting human SET1/MLL family of proteins.Protein science : a publication of the Protein Society · 2017Review
- The importance of detailed epigenomic profiling of different cell types within organs.Epigenomics · 2016Review
- Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse.Blood · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSomatic mutations in epigenetic enzymes are frequently found in cancer tissues. The MLL3 H3K4-specific protein lysine monomethyltransferase is an important epigenetic enzyme, and it is among the most recurrently mutated enzymes in cancers. MLL3 mainly introduces H3K4me1 at enhancers.
resultsWe investigated the enzymatic properties of MLL3 variants that carry somatic cancer mutations. Asn4848 is located at the cofactor binding sites, and the N4848S exchange renders the enzyme inactive. Tyr4884 is part of an aromatic pocket at the active center of the enzyme, and Y4884C converts MLL3 from a monomethyltransferase with substrate preference for H3K4me0 to a trimethyltransferase with H3K4me1 as preferred substrate. Expression of Y4884C leads to aberrant H3K4me3 formation in cells.
conclusionsOur data show that different somatic cancer mutations of MLL3 affect the enzyme activity in distinct and opposing manner highlighting the importance of experimentally studying the effects of somatic cancer mutations in key regulatory enzymes in order to develop and apply targeted tumor therapy.
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Registered trials
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