COMPASS Ascending: Emerging clues regarding the roles of MLL3/KMT2C and MLL2/KMT2D proteins in cancer
Autor: | Andrew K. Dingwall, Richard J. Fagan |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Cancer Research Methyltransferase Genomics medicine.disease_cause Article Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine Neoplasms medicine Animals Humans Epigenetics Gene Genetics Regulation of gene expression biology Histone-Lysine N-Methyltransferase Neoplasm Proteins DNA-Binding Proteins 030104 developmental biology Histone KMT2A Oncology 030220 oncology & carcinogenesis Mutation biology.protein Carcinogenesis Myeloid-Lymphoid Leukemia Protein |
Zdroj: | Cancer Lett |
ISSN: | 0304-3835 |
DOI: | 10.1016/j.canlet.2019.05.024 |
Popis: | The KMT2 (lysine methyltransferase) family of histone modifying proteins play essential roles in regulating developmental pathways, and mutations in the genes encoding these proteins have been strongly linked to many blood and solid tumor cancers. The KMT2A-D proteins are histone 3 lysine 4 (H3K4) methyltransferases embedded in large COMPASS-like complexes important for RNA Polymerase II-dependent transcription. KMT2 mutations were initially associated with pediatric Mixed Lineage Leukemias (MLL) and found to be the result of rearrangements of the MLL1/KMT2A gene at 11q23. Over the past several years, large-scale tumor DNA sequencing studies have revealed the potential involvement of other KMT2 family genes, including heterozygous somatic mutations in the paralogous MLL3/KMT2C and MLL2(4)/KMT2D genes that are now among the most frequently associated with human cancer. Recent studies have provided a better understanding of the potential roles of disrupted KMT2C and KMT2D family proteins in cell growth aberrancy. These findings, together with an examination of cancer genomics databases provide new insights into the contribution of KMT2C/D proteins in epigenetic gene regulation and links to carcinogenesis. |
Databáze: | OpenAIRE |
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