Disease relevance of PRMT1

• Antisense PRMT1 cDNA constructs expressed under the early cytomegalovirus (CMV) promoter were transfected into HeLa cells, and stable transformants were selected [1].
• Here we report that several proteins extracted from HeLa cells were methylated by PRMT1 (protein arginine N-methyltransferease 1) even on a nitrocellulose membrane, while proteins from Escherichia coli are not methylated with this protein [2].
• Although PRMT1 was not found to be hormonally regulated by steroid hormones in breast cancer cells, our results suggest that two variants of PRMT1 are down regulated in breast cancer [3].
• Our data suggest a novel mechanism by which the protein arginine methyltransferase is involved in the control of AR-driven transcription. p44 expression is dramatically enhanced in prostate cancer tissue compared with adjacent benign prostate tissue [4].
• The results presented here suggest that decreased DDAH levels as well as increased PRMT gene expression could cause the elevation of plasma ADMA levels, thereby eliciting hypertension in CKD [5].

Psychiatry related information on PRMT1

• Alternative splicing modulates protein arginine methyltransferase-dependent methylation of fragile X syndrome mental retardation protein [6].

High impact information on PRMT1

• Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53 [7].
• Here we demonstrate arginine methylation of STAT1 by the protein arginine methyl-transferase PRMT1 as a novel requirement for IFNalpha/beta-induced transcription [8].
• Most important, a mutation in the S-adenosyl-l-methionine-binding site of PRMT1 substantially crippled its nuclear receptor coactivator activity [9].
• Our finding reveals Arg 3 of H4 as a novel methylation site by PRMT1 and indicates that Arg 3 methylation plays an important role in transcriptional regulation [9].
• Methylation of Arg 3 by PRMT1 facilitates subsequent acetylation of H4 tails by p300 [9].

Biological context of PRMT1

• HRMT1L3 is a PRMT1 paralogue with highly conserved sequences and exact exon junctions, whereas the PRMT2 orthologues are very diverged [10].
• Finally, endogenous PRMT1 contributes to PGC-1alpha coactivator activity, and to the induction of genes important for mitochondrial biogenesis [11].
• Arginine methylation of MRE11 by PRMT1 is required for DNA damage checkpoint control [12].
• A comparison of substrate specificity reveals that PRMT6 is functionally distinct from two previously characterized type I enzymes, PRMT1 and PRMT4 [13].
• Moreover, CARM1 and PRMT1 acted in a synergistic manner to enhance reporter gene activation by both hormone-dependent and orphan NRs [14].

Anatomical context of PRMT1

• Sam68 was also detected in the cytoplasm of PRMT1-deficient embryonic stem cells [15].
• Flag-IR1B4 fusion proteins bind to the isolated IFNAR1 intracytoplasmic domain produced in Escherichia coli, as well as to the intact IFNAR1 chain extracted by detergent from human U266 cell membranes [16].
• Remarkably, PRMT1, whose methylation activity on histone H4 strongly correlates with induction of HNF4 target genes in differentiating enterocytes, regulates HNF4 activity through a bipartite mechanism [17].
• Our results thus reveal the role of a PRMT in protein localization in germ cells [18].
• All PRMT isoforms investigated were detected at the mRNA and protein level in mouse lung, and were localized primarily to the bronchial and alveolar epithelium [19].

Associations of PRMT1 with chemical compounds

• A(63-)VLD(-65) to AAA mutation of PRMT1 suppressed the methylation of recombinant SAMT1 and other RGG proteins in the HeLa extracts [2].
• The methyl transferase PRMT1 functions as co-activator of farnesoid X receptor (FXR)/9-cis retinoid X receptor and regulates transcription of FXR responsive genes [20].
• Here we describe the crystal structure of rat PRMT1 in complex with the reaction product AdoHcy and a 19 residue substrate peptide containing three arginines [21].
• Moreover, inhibition of methyltransferase activity, pre-acetylation, or activation of the enzyme PAD4 attenuated retinoid-regulated gene expression, while overexpression of PRMT1, a methyltransferase, enhanced retinoid responsiveness [22].
• SET-mediated Promoter Hypoacetylation Is a Prerequisite for Coactivation of the Estrogen-responsive pS2 Gene by PRMT1 [23].

Physical interactions of PRMT1

• Our findings identify the GAR motif as a region required for 53BP1 DNA binding activity and as the site of methylation by PRMT1 [24].
• A protein-arginine methyltransferase binds to the intracytoplasmic domain of the IFNAR1 chain in the type I interferon receptor [16].
• Methylation of DNA polymerase beta by protein arginine methyltransferase 1 regulates its binding to proliferating cell nuclear antigen [25].

Enzymatic interactions of PRMT1

• Arginine methylation in RNA-binding proteins containing arginine- and glycine-rich RGG motifs is catalyzed by specific protein arginine N-methyltransferase in cells [26].

Regulatory relationships of PRMT1

• Asymmetric Arginine Dimethylation of Heterogeneous Nuclear Ribonucleoprotein K by Protein-arginine Methyltransferase 1 Inhibits Its Interaction with c-Src [27].

Other interactions of PRMT1

• PRMT5 appears to have lower specific enzyme activity than PRMT1 [28].
• Using an immunofluorescence analysis, we determined that ILF3 and PRMT1 co-localize in the nucleus [29].
• The antiproliferative effect of IFN-beta was also reduced up to fivefold in the clones with low PRMT1 expression [1].
• 53BP1 oligomerization is independent of its methylation by PRMT1 [30].
• PRMT7, a new protein arginine methyltransferase that synthesizes symmetric dimethylarginine [31].

Analytical, diagnostic and therapeutic context of PRMT1

• Moreover, PRMT1 and ILF3 co-precipitate in immunoprecipitation assays and can be isolated together in "pull-down" experiments using recombinant fusion proteins [29].
• Chromatin immunoprecipitation assay suggests that 6-ECDCA induces both the recruitment of PRMT1 and the H4 methylation to the promoter of BSEP and SHP genes [20].
• Western blot analyses of zebrafish tissue extracts confirmed the expression of some PRMT proteins in zebra fish [10].
• In summary, our data show that the yeast two-hybrid assay is an effective system for identifying novel PRMT arginine-methylation substrates and may be successfully applied to other members of the growing family of PRMTs [32].
• Using quantitative real-time PCR, we examined the expression of Hcp1 and other intestinal iron-transporting proteins in male C57BL/6 mice with experimentally altered iron homeostasis [33].

References