Protein arginine methyltransferases and cancer

Yang, Yanzhong; Bedford, Mark T.

doi:10.1038/nrc3409

Cited by 875 publications

(1,069 citation statements)

References 193 publications

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“…We are also learning the importance of crosstalk between protein and DNA methylation reactions (9) and among protein methylation, phosphorylation, acetylation, and ubiquitination reactions (10)(11)(12). Finally, we are discovering how alterations in protein methylation pathways can lead to human pathology, particularly in cancer (13)(14)(15).…”

Section: Regulation Of Biological Function By Protein Methylation Reamentioning

confidence: 99%

“…That proteins are methylated by the products of genes that have often been conserved throughout the evolutionary development of organisms suggests that a full understanding of the biology of an organism needs to include an appreciation of these modifications and their functions. As we learn more from each new protein methylation system described, the range of functional roles also increases, and we are provided new targets for therapeutic intervention into human diseases (13,27).…”

Section: Regulation Of Biological Function By Protein Methylation Reamentioning

confidence: 99%

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The ribosome: A hot spot for the identification of new types of protein methyltransferases

Clarke¹

2018

Journal of Biological Chemistry

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Cellular physiology depends on the alteration of protein structures by covalent modification reactions. Using a combination of bioinformatic, genetic, biochemical, and mass spectrometric approaches, it has been possible to probe ribosomal proteins from the yeast Saccharomyces cerevisiae for posttranslationally methylated amino acid residues and for the enzymes that catalyze these modifications. These efforts have resulted in the identification and characterization of the first protein histidine methyltransferase, the first N-terminal protein methyltransferase, two unusual types of protein arginine methyltransferases, and a new type of cysteine methylation. Two of these enzymes may modify their substrates during ribosomal assembly because the final methylated histidine and arginine residues are buried deep within the ribosome with contacts only with RNA. Two of these modifications occur broadly in eukaryotes, including humans, while the others demonstrate a more limited phylogenetic range. Analysis of strains where the methyltransferase genes are deleted has given insight into the physiological roles of these modifications. These reactions described here add diversity to the modifications that generate the typical methylated lysine and arginine residues previously described in histones and other proteins. Regulation of biological function by protein methylation reactionsIt is more and more apparent just how much of biological function is dependent upon posttranslational modifications (1). The human genome encodes some 900 enzymes catalyzing just protein phosphorylation or ubiquitination (2,3). However, it is now clear that methyl groups can stand beside phosphate groups and ubiquitin as major players in controlling the physiological functions of proteins. We are beginning to understand how the much greater diversity of protein methylation reactions can give rise to a greater diversity of function (1,4-8). We are also learning the importance of crosstalk between protein and DNA methylation reactions (9) and among protein methylation, phosphorylation, acetylation, and ubiquitination reactions (10-12). Finally, we are discovering how alterations in protein methylation pathways can lead to human pathology, particularly in cancer (13-15).The collection of over sixty human protein arginine and lysine methyltransferases that leave histone "marks" recognized by reader proteins to guide gene expression are perhaps the poster children for the importance of protein methyltransferases (16-17). However, recent work has emphasized the importance of methylating non-histone substrates at these residues, particularly ribosomal proteins, translation factors, and transcription factors in a wide variety of organisms (7,8,15,18,19). Furthermore, the methylation of lysine and arginine residues represents just the tip of the iceberg in protein methylation -modifications have also been established at histidine, modified histidine (diphthamide), glutamate, glutamine, asparagine, Lisoaspartate, D-aspartate, cysteine, isoprenylcysteine, me...

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Section: Regulation Of Biological Function By Protein Methylation Reamentioning

confidence: 99%

Section: Regulation Of Biological Function By Protein Methylation Reamentioning

confidence: 99%

The ribosome: A hot spot for the identification of new types of protein methyltransferases

Clarke¹

2018

Journal of Biological Chemistry

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“…A large family of 60 histone methyltransferases, including histone lysine methyltransferases (KMTs) and protein/histone arginine methyltransferases (PRMTs), were identified in humans, and the biochemical and biologic functions of many methyltransferases have been characterized. 69,75 (Fig. 1).…”

Section: Kmts and Prmtsmentioning

confidence: 99%

“…For example, PRMT1 is necessary for leukemic transformation, which requires co-recruitment of KDM4C, an H3K9 demethylase. 75,104 Lysine demethylases Histone methylation is also dynamically controlled by histone/ protein lysine demethylases (KDMs), enzymes that remove the methyl group(s) from a methylated lysine side chain (Fig. 1).…”

Section: H3k9mtsmentioning

confidence: 99%

Epigenetic modification in chromatin machinery and its deregulation in pediatric brain tumors: Insight into epigenetic therapies

Maury

Hashizume

2017

Epigenetics

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Malignancies are characterized by the reprogramming of epigenetic patterns. This reprogramming includes gains or losses in DNA methylation and disruption of normal patterns of covalent histone modifications, which are associated with changes in chromatin remodeling processes. This review will focus on the mechanisms underlying this reprogramming and, specifically, on the role of histone modification in chromatin machinery and the modifications in epigenetic processes occurring in brain cancer, with a specific focus on epigenetic therapies for pediatric brain tumors.

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“…However, compared with histone lysine methylation, the influence of histone arginine methylation on gene regulation has remained largely unexplored. The physiological functions of histone arginine methylation play roles in numerous processes, such as cell differentiation, embryonic development, and carcinogenesis (14,15). In mammals, nine members of the PRMT family catalyze mono-, asymmetric di-, and symmetric dimethylated arginine residues (16).Unlike the other members, PRMT7 is unique owing to its controversial catalyzed arginine types.…”

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confidence: 99%

Histone Arginine Methylation by PRMT7 Controls Germinal Center Formation via Regulating Bcl6 Transcription

Ying

Mei

Zhang

et al. 2015

The Journal of Immunology

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B cells are the center of humoral immunity and produce Abs to protect against foreign Ags. B cell defects lead to diseases such as leukemia and lymphomas. Histone arginine methylation is important for regulating gene activation and silencing in cells. Although the process commonly exists in mammalian cells, its roles in B cells are unknown. To explore the effects of aberrant histone arginine methylation on B cells, we generated mice with a B cell–specific knockout of PRMT7, a member of the methyltransferases that mediate arginine methylation of histones. In this article, we showed that the loss of PRMT7 led to decreased mature marginal zone B cells and increased follicular B cells and promoted germinal center formation after immunization. Furthermore, mice lacking PRMT7 expression in B cells secreted low levels of IgG1 and IgA. Abnormal expression of germinal center genes (i.e., Bcl6, Prdm1, and Irf4) was detected in conditional knockout mice. By overexpressing PRMT7 in the Raji and A20 cell lines derived from B cell lymphomas, we validated the fact that PRMT7 negatively regulated Bcl6 expression. Using chromatin immunoprecipitation–PCR, we found that PRMT7 could recruit H4R3me1 and symmetric H4R3me2 to the Bcl6 promoter. These results provide evidence for the important roles played by PRMT7 in germinal center formation.

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Protein arginine methyltransferases and cancer

Cited by 875 publications

References 193 publications

The ribosome: A hot spot for the identification of new types of protein methyltransferases

The ribosome: A hot spot for the identification of new types of protein methyltransferases

Epigenetic modification in chromatin machinery and its deregulation in pediatric brain tumors: Insight into epigenetic therapies

Histone Arginine Methylation by PRMT7 Controls Germinal Center Formation via Regulating Bcl6 Transcription

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