FBXO11/PRMT9, a new protein arginine methyltransferase, symmetrically dimethylates arginine residues

Cook, Jeffry R.; Lee, Jin-Hyung; Yang, Zhihong; Krause, Christopher D.; Herth, Nicole; Hoffmann, Ralf; Pestka, Sidney

doi:10.1016/j.bbrc.2006.01.167

Cited by 123 publications

(107 citation statements)

References 38 publications

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“…In mammals, six type I PRMT enzymes, such as PRMT1 [2], PRMT2 [3], PRMT3 [4], CARM1 (PRMT4) [5], PRMT6 [6] and PRMT8, have been identified, and type II enzymes identified to date include the Janus kinase-binding protein JBP1/PRMT5 [7], and PRMT7 [8,9]. The recently identified FBXO11/PRMT9 should belong to type II PRMT family although it contains a unique N-terminal F-box domain that does not appear in the other known PRMT enzymes [10]. Structurally, PRMT proteins possess double E and THW loops, an S-adenosylmethionine binding site (motif I), a catalytically active region (motif III), and two function-unknown motifs termed ''post-I'' and ''motif II'' [11].…”

Section: Introductionmentioning

confidence: 99%

Molecular characterisation and inductive expression of a fish protein arginine methyltransferase 1 gene in response to virus infection

Caiwen

Zhang

Lü

et al. 2007

Fish & Shellfish Immunology

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Section: Introductionmentioning

confidence: 99%

Molecular characterisation and inductive expression of a fish protein arginine methyltransferase 1 gene in response to virus infection

Caiwen

Zhang

Lü

et al. 2007

Fish & Shellfish Immunology

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“…Although methylation of arginine residues was discovered more than 30 years ago [1], the functional significance of methylated arginine has been demonstrated only recently. To date, nine protein arginine methyltransferases (PRMTs) have been isolated and classified into two groups: type I and type II enzymes [2,3]. While both types can catalyze x-N Gmonomethylation of arginine as an intermediate, type I enzymes (PRMT1, PRMT3, PRMT4, PRMT6 and PRMT8) promote asymmetric x-N G ,N G -dimethylation of arginine residue, whereas type II enzymes (PRMT5, PRMT7 and PRMT9) catalyze the formation of symmetric x-N G ,N 0G -dimethylarginine.…”

Section: Introductionmentioning

confidence: 99%

“…While both types can catalyze x-N Gmonomethylation of arginine as an intermediate, type I enzymes (PRMT1, PRMT3, PRMT4, PRMT6 and PRMT8) promote asymmetric x-N G ,N G -dimethylation of arginine residue, whereas type II enzymes (PRMT5, PRMT7 and PRMT9) catalyze the formation of symmetric x-N G ,N 0G -dimethylarginine. No enzymatic activity has been documented for PRMT2 in spite of its structural similarity to other PRMT family members [2,3]. PRMT1-deficient mice die at E6.5, whereas PRMT4-deficient mice can survive till late embryogenesis or perinatally.…”

Section: Introductionmentioning

confidence: 99%

Methylation of Smad6 by protein arginine N‐methyltransferase 1

et al. 2006

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Signal transduction pathways utilize posttranslational modifications to regulate the activity of their components in a temporal-spatial and efficient fashion. Arginine methylation is one of the posttranslational modifications that can result in monomethylated-, asymmetric dimethylated-and/or symmetric dimethylated-arginine residues in proteins. Here we demonstrate that inhibitory-Smads (Smad6 and Smad7), but not receptorregulated-(R-)Smads and the common-partner Smad4, can be methylated by protein arginine N-methyltransferase (PRMT)1. Using mass-spectrometric analysis, we found that PRMT1 dimethylates arginine 74 (Arg 74 ) in mouse Smad6. PRMT1 interacts with the N-terminal domain of Smad6 in which Arg 74 residue is located. Assays examined so far have shown no significant differences between the functions of Smad6 and those of methylation-defective Smad6 (Smad6R74A). Both wild-type and Smad6R74A were equally efficient in blocking BMP-induced growth arrest upon their ectopic expression in HS-72 mouse Bcell hybridoma cells.

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“…To date there are 11 PRMTs, and except for PRMT2, PRMT10, and PRMT11, they all have the ability to catalyze arginine methylation (6,9,21,28,29,30,35). Among all PRMTs, only PRMT4/CARM1 and PRMT5 have been shown to interact with ATP-dependent chromatin remodelers (22,28,29,36).…”

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confidence: 99%

Protein Arginine Methyltransferase 5 Suppresses the Transcription of the RB Family of Tumor Suppressors in Leukemia and Lymphoma Cells

Wang

Pal

Sif

2008

Molecular and Cellular Biology

229

225

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The proper epigenetic modification of chromatin by protein arginine methyltransferases (PRMTs) is crucial for normal cell growth and health. The human SWI/SNF-associated PRMT5 is involved in the transcriptional repression of target genes by directly methylating H3R8 and H4R3. To further understand the impact of PRMT5-mediated histone methylation on cancer, we analyzed its expression in normal and transformed human B lymphocytes. Our findings reveal that PRMT5 protein levels are enhanced in various human lymphoid cancer cells, including transformed chronic lymphocytic leukemia (B-CLL) cell lines. PRMT5 overexpression is caused by the altered expression of the PRMT5-specific microRNAs 19a, 25, 32, 92, 92b, and 96 and results in the increased global symmetric methylation of H3R8 and H4R3. An evaluation of both epigenetic marks at PRMT5 target genes such as RB1 (p105), RBL1 (p107), and RBL2 (p130) showed that promoters H3R8 and H4R3 are hypermethylated, which in turn triggers pocket protein transcriptional repression. Furthermore, reducing PRMT5 expression in WaC3CD5 B-CLL cells abolishes H3R8 and H4R3 hypermethylation, restores RBL2 expression, and inhibits cancer cell proliferation. These results indicate that PRMT5 overexpression epigenetically alters the transcription of key tumor suppressor genes and suggest a causal role of the elevated symmetric methylation of H3R8 and H4R3 at the RBL2 promoter in transformed B-lymphocyte pathology.Enzymes that modify chromatin via arginine methylation have different effects on gene expression, depending on whether they catalyze either the symmetric or asymmetric dimethylation of histones (20,31). Recent work has clearly established a link between the aberrant expression of chromatinmodifying enzymes and cancer; however, the impact protein arginine methyltransferases (PRMTs) have on cell growth and proliferation has only begun to be appreciated. The role PRMTs play in cancer epigenetics remains unexplored, and it is essential to unravel how histone arginine methylation influences cancer. Previous studies have shown that the expression of EZH2, the catalytic subunit of PRC2/3, is altered in cancer cells (19,32,40,41). Similarly, several reports have shown that the interplay and cross-talk between chromatin-modifying enzymes is necessary for the efficient regulation of gene expression, and that changes that affect the activity and/or targeting of chromatin remodelers can trigger cancer (13, 23).Histone methylation has emerged as an important epigenetic modification in the control of chromatin structure and gene expression, and there is little doubt that different epigenetic marks act either synergistically or antagonistically to specify transcriptional performance in various chromatin regions (13). The methylation of histones can be found on both lysine and arginine residues, and both modifications are introduced by SET and PRMT enzymes, respectively. Just like SET proteins, which either can induce or repress transcription, PRMTs either can induce or inhibit transcription depen...

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FBXO11/PRMT9, a new protein arginine methyltransferase, symmetrically dimethylates arginine residues

Cited by 123 publications

References 38 publications

Molecular characterisation and inductive expression of a fish protein arginine methyltransferase 1 gene in response to virus infection

Molecular characterisation and inductive expression of a fish protein arginine methyltransferase 1 gene in response to virus infection

Methylation of Smad6 by protein arginine N‐methyltransferase 1

Protein Arginine Methyltransferase 5 Suppresses the Transcription of the RB Family of Tumor Suppressors in Leukemia and Lymphoma Cells

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