MLL5 (KMT2E): structure, function, and clinical relevance
The mixed lineage leukemia (MLL) family of genes, also known as the lysine N-methyltransferase 2 (KMT2) family, are homologous to the evolutionarily conserved trithorax group that plays critical roles in the regulation of homeotic gene (HOX) expression and embryonic development. MLL5, assigned as KM...
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Published in | Cellular and molecular life sciences : CMLS Vol. 74; no. 13; pp. 2333 - 2344 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
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Cham
Springer International Publishing
01.07.2017
Springer Nature B.V |
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Abstract | The mixed lineage leukemia (MLL) family of genes, also known as the lysine N-methyltransferase 2 (KMT2) family, are homologous to the evolutionarily conserved trithorax group that plays critical roles in the regulation of homeotic gene (HOX) expression and embryonic development. MLL5, assigned as KMT2E on the basis of its SET domain homology, was initially categorized under MLL (KMT2) family together with other six SET methyltransferase domain proteins (KMT2A–2D and 2F–2G). However, emerging evidence suggests that MLL5 is distinct from the other MLL (KMT2) family members, and the protein it encodes appears to lack intrinsic histone methyltransferase (HMT) activity towards histone substrates. MLL5 has been reported to play key roles in diverse biological processes, including cell cycle progression, genomic stability maintenance, adult hematopoiesis, and spermatogenesis. Recent studies of MLL5 variants and isoforms and putative MLL5 homologs in other species have enriched our understanding of the role of MLL5 in gene expression regulation, although the mechanism of action and physiological function of MLL5 remains poorly understood. In this review, we summarize recent research characterizing the structural features and biological roles of MLL5, and we highlight the potential implications of MLL5 dysfunction in human disease. |
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AbstractList | The mixed lineage leukemia (MLL) family of genes, also known as the lysine N-methyltransferase 2 (KMT2) family, are homologous to the evolutionarily conserved trithorax group that plays critical roles in the regulation of homeotic gene (HOX) expression and embryonic development. MLL5, assigned as KMT2E on the basis of its SET domain homology, was initially categorized under MLL (KMT2) family together with other six SET methyltransferase domain proteins (KMT2A-2D and 2F-2G). However, emerging evidence suggests that MLL5 is distinct from the other MLL (KMT2) family members, and the protein it encodes appears to lack intrinsic histone methyltransferase (HMT) activity towards histone substrates. MLL5 has been reported to play key roles in diverse biological processes, including cell cycle progression, genomic stability maintenance, adult hematopoiesis, and spermatogenesis. Recent studies of MLL5 variants and isoforms and putative MLL5 homologs in other species have enriched our understanding of the role of MLL5 in gene expression regulation, although the mechanism of action and physiological function of MLL5 remains poorly understood. In this review, we summarize recent research characterizing the structural features and biological roles of MLL5, and we highlight the potential implications of MLL5 dysfunction in human disease. |
Author | Zhang, Xiaoming Deng, Lih-Wen Novera, Wisna Zhang, Yan |
Author_xml | – sequence: 1 givenname: Xiaoming surname: Zhang fullname: Zhang, Xiaoming organization: Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore – sequence: 2 givenname: Wisna surname: Novera fullname: Novera, Wisna organization: Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore – sequence: 3 givenname: Yan surname: Zhang fullname: Zhang, Yan organization: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences – sequence: 4 givenname: Lih-Wen orcidid: 0000-0002-4985-7844 surname: Deng fullname: Deng, Lih-Wen email: bchdlw@nus.edu.sg organization: Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, National University Cancer Institute, National University Health System |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28188343$$D View this record in MEDLINE/PubMed |
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Keywords | Cell division Hematopoietic stem cell differentiation Histone methylation Leukemia PHD finger Cancer |
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Snippet | The mixed lineage leukemia (MLL) family of genes, also known as the lysine N-methyltransferase 2 (KMT2) family, are homologous to the evolutionarily conserved... |
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SubjectTerms | Animals Biochemistry Biological activity Biomedical and Life Sciences Biomedicine Cell Biology Cell Cycle Clinical trials Disease DNA-Binding Proteins - chemistry DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Embryogenesis Embryonic growth stage Enrichment Evolution Gene expression Gene regulation Genes Genomic Instability Hematopoiesis Histone methyltransferase Homology Humans Isoforms Leukemia Life Sciences Lysine Maintenance Mutation - genetics N-Methyltransferase Protein Isoforms - chemistry Protein Isoforms - genetics Protein Isoforms - metabolism Proteins Review Reviews Spermatogenesis Stability Structure-function relationships Substrates Transcription |
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Title | MLL5 (KMT2E): structure, function, and clinical relevance |
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