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PMID: 19164444 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Minireview: protein arginine methylation of nonhistone proteins in transcriptional regulation.

Molecular endocrinology (Baltimore, Md.) ·Vol. 23 ·No. 4 ·2009-04-00 ·Pages 425-33

Lee YH, Stallcup MR

Abstract

Endocrine regulation frequently culminates in altered transcription of specific genes. The signal transduction pathways, which transmit the endocrine signal from cell surface to the transcription machinery, often involve posttranslational modifications of proteins. Although phosphorylation has been by far the most widely studied protein modification, recent studies have indicated important roles for other types of modification, including protein arginine methylation. Ten different protein arginine methyltransferase (PRMT) family members have been identified in mammalian cells, and numerous substrates are being identified for these PRMTs. Whereas major attention has been focused on the methylation of histones and its role in chromatin remodeling and transcriptional regulation, there are many nonhistone substrates methylated by PRMTs. This review primarily focuses on recent progress on the roles of the nonhistone protein methylation in transcription. Protein methylation of coactivators, transcription factors, and signal transducers, among other proteins, plays important roles in transcriptional regulation. Protein methylation may affect protein-protein interaction, protein-DNA or protein-RNA interaction, protein stability, subcellular localization, or enzymatic activity. Thus, protein arginine methylation is critical for regulation of transcription and potentially for various physiological/pathological processes.

MeSH Terms
Animals DNA-Binding Proteins/metabolism Gene Expression Regulation Methylation Protein-Arginine N-Methyltransferases/metabolism RNA-Binding Proteins/metabolism Transcription, Genetic
Chemicals
DNA-Binding Proteins RNA-Binding Proteins Protein-Arginine N-Methyltransferases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Lee Young-Ho
Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Los Angeles, California 90089-9176, USA.
Stallcup Michael R
References (87)
87 references, click to expand
  1. Detection of arginine dimethylated peptides by parallel precursor ion scanning mass spectrometry in positive ion mode.
    Anal Chem. 2003 Jul 1;75(13):3107-14 PMID: 12964758
  2. Arginine methylation of STAT1 modulates IFNalpha/beta-induced transcription.
    Cell. 2001 Mar 9;104(5):731-41 PMID: 11257227
  3. Regulation of coactivator complex assembly and function by protein arginine methylation and demethylimination.
    Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3611-6 PMID: 15731352
  4. Histone citrullination by protein arginine deiminase: is arginine methylation a green light or a roadblock?
    ACS Chem Biol. 2006 Aug 22;1(7):433-41 PMID: 17168521
  5. How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers.
    Nat Struct Mol Biol. 2007 Nov;14(11):1025-1040 PMID: 17984965
  6. Lipopolysaccharide-induced methylation of HuR, an mRNA-stabilizing protein, by CARM1. Coactivator-associated arginine methyltransferase.
    J Biol Chem. 2002 Nov 22;277(47):44623-30 PMID: 12237300
  7. Two functional modes of a nuclear receptor-recruited arginine methyltransferase in transcriptional activation.
    Mol Cell. 2006 Oct 20;24(2):233-43 PMID: 17052457
  8. Chromatin modifications and their function.
    Cell. 2007 Feb 23;128(4):693-705 PMID: 17320507
  9. Control of the DNA methylation system component MBD2 by protein arginine methylation.
    Mol Cell Biol. 2006 Oct;26(19):7224-35 PMID: 16980624
  10. Methylation of arginine residues interferes with citrullination by peptidylarginine deiminases in vitro.
    J Mol Biol. 2007 Apr 6;367(4):1118-29 PMID: 17303166
  11. The GAR motif of 53BP1 is arginine methylated by PRMT1 and is necessary for 53BP1 DNA binding activity.
    Cell Cycle. 2005 Dec;4(12):1834-41 PMID: 16294045
  12. Distribution of NG, NG,-dimethylarginine in nuclear protein fractions.
    Biochem Biophys Res Commun. 1977 Feb 7;74(3):969-76 PMID: 843361
  13. Steroid hormone receptors: many actors in search of a plot.
    Cell. 1995 Dec 15;83(6):851-7 PMID: 8521509
  14. Histone demethylation by a family of JmjC domain-containing proteins.
    Nature. 2006 Feb 16;439(7078):811-6 PMID: 16362057
  15. Methylation of MRE11 regulates its nuclear compartmentalization.
    Cell Cycle. 2005 Jul;4(7):981-9 PMID: 15970667
  16. Arginine methylation of the histone H3 tail impedes effector binding.
    J Biol Chem. 2008 Feb 8;283(6):3006-3010 PMID: 18077460
  17. A proteomic analysis of arginine-methylated protein complexes.
    Mol Cell Proteomics. 2003 Dec;2(12):1319-30 PMID: 14534352
  18. Histone deimination antagonizes arginine methylation.
    Cell. 2004 Sep 3;118(5):545-53 PMID: 15339660
  19. CARM1 regulates estrogen-stimulated breast cancer growth through up-regulation of E2F1.
    Cancer Res. 2008 Jan 1;68(1):301-6 PMID: 18172323
  20. Methylation of Xilf3 by Xprmt1b alters its DNA, but not RNA, binding activity.
    Biochemistry. 2008 Aug 12;47(32):8350-7 PMID: 18636753
  21. Regulation of transcription by a protein methyltransferase.
    Science. 1999 Jun 25;284(5423):2174-7 PMID: 10381882
  22. PRMT3 is a distinct member of the protein arginine N-methyltransferase family. Conferral of substrate specificity by a zinc-finger domain.
    J Biol Chem. 2000 Oct 20;275(42):32974-82 PMID: 10931850
  23. The arginine methyltransferase CARM1 regulates the coupling of transcription and mRNA processing.
    Mol Cell. 2007 Jan 12;25(1):71-83 PMID: 17218272
  24. JMJD6 is a histone arginine demethylase.
    Science. 2007 Oct 19;318(5849):444-7 PMID: 17947579
  25. Structure of the predominant protein arginine methyltransferase PRMT1 and analysis of its binding to substrate peptides.
    Structure. 2003 May;11(5):509-20 PMID: 12737817
  26. Protein arginine methylation in health and disease.
    Biotechnol Annu Rev. 2008;14:203-24 PMID: 18606365
  27. RNA and protein interactions modulated by protein arginine methylation.
    Prog Nucleic Acid Res Mol Biol. 1998;61:65-131 PMID: 9752719
  28. Phosphorylation-mediated inactivation of coactivator-associated arginine methyltransferase 1.
    Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12318-23 PMID: 17640894
  29. Synthesis and biological validation of novel synthetic histone/protein methyltransferase inhibitors.
    ChemMedChem. 2007 Jul;2(7):987-91 PMID: 17458842
  30. Human SWI/SNF-associated PRMT5 methylates histone H3 arginine 8 and negatively regulates expression of ST7 and NM23 tumor suppressor genes.
    Mol Cell Biol. 2004 Nov;24(21):9630-45 PMID: 15485929
  31. Methylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity.
    Genes Dev. 2008 Mar 1;22(5):640-53 PMID: 18316480
  32. Identification and characterization of two putative human arginine methyltransferases (HRMT1L1 and HRMT1L2).
    Genomics. 1998 Mar 15;48(3):330-40 PMID: 9545638
  33. A glycine-arginine domain in control of the human MRE11 DNA repair protein.
    Mol Cell Biol. 2008 May;28(9):3058-69 PMID: 18285453
  34. Arginine methylation of MRE11 by PRMT1 is required for DNA damage checkpoint control.
    Genes Dev. 2005 Mar 15;19(6):671-6 PMID: 15741314
  35. State of the arg: protein methylation at arginine comes of age.
    Cell. 2001 Jul 13;106(1):5-8 PMID: 11461695
  36. Historical review: the field of protein methylation.
    Trends Biochem Sci. 2007 Mar;32(3):146-52 PMID: 17291768
  37. The expanding cosmos of nuclear receptor coactivators.
    Cell. 2006 May 5;125(3):411-4 PMID: 16678083
  38. Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties.
    Mol Cell. 2003 Apr;11(4):1055-66 PMID: 12718890
  39. Visualizing chromatin dynamics in intact cells.
    Biochim Biophys Acta. 2008 Nov;1783(11):2044-51 PMID: 18675855
  40. Surface-scanning mutational analysis of protein arginine methyltransferase 1: roles of specific amino acids in methyltransferase substrate specificity, oligomerization, and coactivator function.
    Mol Endocrinol. 2007 Jun;21(6):1381-93 PMID: 17426288
  41. The novel human protein arginine N-methyltransferase PRMT6 is a nuclear enzyme displaying unique substrate specificity.
    J Biol Chem. 2002 Feb 1;277(5):3537-43 PMID: 11724789
  42. In situ generation of a bisubstrate analogue for protein arginine methyltransferase 1.
    J Am Chem Soc. 2008 Apr 9;130(14):4574-5 PMID: 18338885
  43. Functional insights from structures of coactivator-associated arginine methyltransferase 1 domains.
    EMBO J. 2007 Oct 17;26(20):4391-401 PMID: 17882262
  44. Requirement for multiple domains of the protein arginine methyltransferase CARM1 in its transcriptional coactivator function.
    J Biol Chem. 2002 Nov 29;277(48):46066-72 PMID: 12351636
  45. Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors.
    Bioorg Med Chem. 2008 Jan 15;16(2):739-45 PMID: 17964793
  46. A methylation-mediator complex in hormone signaling.
    Genes Dev. 2004 Jan 15;18(2):144-56 PMID: 14729568
  47. Sensors and signals: a coactivator/corepressor/epigenetic code for integrating signal-dependent programs of transcriptional response.
    Genes Dev. 2006 Jun 1;20(11):1405-28 PMID: 16751179
  48. Cracking the coregulator codes.
    Curr Opin Cell Biol. 2008 Jun;20(3):310-5 PMID: 18499426
  49. The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase.
    J Biol Chem. 1996 Jun 21;271(25):15034-44 PMID: 8663146
  50. A transcriptional switch mediated by cofactor methylation.
    Science. 2001 Dec 21;294(5551):2507-11 PMID: 11701890
  51. DAL-1/4.1B tumor suppressor interacts with protein arginine N-methyltransferase 3 (PRMT3) and inhibits its ability to methylate substrates in vitro and in vivo.
    Oncogene. 2004 Oct 14;23(47):7761-71 PMID: 15334060
  52. Methylation at arginine 17 of histone H3 is linked to gene activation.
    EMBO Rep. 2002 Jan;3(1):39-44 PMID: 11751582
  53. Arginine methylation an emerging regulator of protein function.
    Mol Cell. 2005 Apr 29;18(3):263-72 PMID: 15866169
  54. Insights into histone code syntax from structural and biochemical studies of CARM1 methyltransferase.
    EMBO J. 2007 Oct 17;26(20):4402-12 PMID: 17882261
  55. A protein-arginine methyltransferase binds to the intracytoplasmic domain of the IFNAR1 chain in the type I interferon receptor.
    EMBO J. 1997 Jan 15;16(2):260-6 PMID: 9029147
  56. The testis-specific factor CTCFL cooperates with the protein methyltransferase PRMT7 in H19 imprinting control region methylation.
    PLoS Biol. 2006 Oct;4(11):e355 PMID: 17048991
  57. The RXR heterodimers and orphan receptors.
    Cell. 1995 Dec 15;83(6):841-50 PMID: 8521508
  58. Small molecule regulators of protein arginine methyltransferases.
    J Biol Chem. 2004 Jun 4;279(23):23892-9 PMID: 15056663
  59. PABP1 identified as an arginine methyltransferase substrate using high-density protein arrays.
    EMBO Rep. 2002 Mar;3(3):268-73 PMID: 11850402
  60. Identification of proteins interacting with the RNAPII FCP1 phosphatase: FCP1 forms a complex with arginine methyltransferase PRMT5 and it is a substrate for PRMT5-mediated methylation.
    FEBS Lett. 2005 Jan 31;579(3):683-9 PMID: 15670829
  61. Role of protein methylation in regulation of transcription.
    Endocr Rev. 2005 Apr;26(2):147-70 PMID: 15479858
  62. Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter.
    Cell. 2003 Dec 12;115(6):751-63 PMID: 14675539
  63. Arginine methylation at a glance.
    J Cell Sci. 2007 Dec 15;120(Pt 24):4243-6 PMID: 18057026
  64. Signaling within a coactivator complex: methylation of SRC-3/AIB1 is a molecular switch for complex disassembly.
    Mol Cell Biol. 2006 Nov;26(21):7846-57 PMID: 16923966
  65. Regulation of estrogen rapid signaling through arginine methylation by PRMT1.
    Mol Cell. 2008 Jul 25;31(2):212-21 PMID: 18657504
  66. Control of CBP co-activating activity by arginine methylation.
    EMBO J. 2002 Oct 15;21(20):5457-66 PMID: 12374746
  67. Arginine methylation of RNA helicase a determines its subcellular localization.
    J Biol Chem. 2004 May 28;279(22):22795-8 PMID: 15084609
  68. PRMT 3, a type I protein arginine N-methyltransferase that differs from PRMT1 in its oligomerization, subcellular localization, substrate specificity, and regulation.
    J Biol Chem. 1998 Jul 3;273(27):16935-45 PMID: 9642256
  69. The activity and stability of the transcriptional coactivator p/CIP/SRC-3 are regulated by CARM1-dependent methylation.
    Mol Cell Biol. 2007 Jan;27(1):120-34 PMID: 17043108
  70. Suppression of receptor interacting protein 140 repressive activity by protein arginine methylation.
    EMBO J. 2006 Nov 1;25(21):5094-104 PMID: 17053781
  71. Methylation of Smad6 by protein arginine N-methyltransferase 1.
    FEBS Lett. 2006 Dec 11;580(28-29):6603-11 PMID: 17118358
  72. Regulation of protein arginine methyltransferase 8 (PRMT8) activity by its N-terminal domain.
    J Biol Chem. 2007 Dec 14;282(50):36444-53 PMID: 17925405
  73. Arginine methylation of hnRNP K enhances p53 transcriptional activity.
    FEBS Lett. 2008 May 28;582(12):1761-5 PMID: 18472002
  74. Human PAD4 regulates histone arginine methylation levels via demethylimination.
    Science. 2004 Oct 8;306(5694):279-83 PMID: 15345777
  75. Targeted recruitment of a histone H4-specific methyltransferase by the transcription factor YY1.
    Genes Dev. 2003 Apr 15;17(8):1019-29 PMID: 12704081
  76. The roles of protein-protein interactions and protein methylation in transcriptional activation by nuclear receptors and their coactivators.
    J Steroid Biochem Mol Biol. 2003 Jun;85(2-5):139-45 PMID: 12943698
  77. Activation of nuclear receptor coactivator PGC-1alpha by arginine methylation.
    Genes Dev. 2005 Jun 15;19(12):1466-73 PMID: 15964996
  78. Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization.
    Biochemistry. 2006 Oct 3;45(39):11727-36 PMID: 17002273
  79. Hormone-dependent, CARM1-directed, arginine-specific methylation of histone H3 on a steroid-regulated promoter.
    Curr Biol. 2001 Dec 11;11(24):1981-5 PMID: 11747826
  80. Regulation of histone methylation by demethylimination and demethylation.
    Nat Rev Mol Cell Biol. 2007 Apr;8(4):307-18 PMID: 17342184
  81. A fluoroacetamidine-based inactivator of protein arginine deiminase 4: design, synthesis, and in vitro and in vivo evaluation.
    J Am Chem Soc. 2006 Feb 1;128(4):1092-3 PMID: 16433522
  82. Arginine methylation facilitates the nuclear export of hnRNP proteins.
    Genes Dev. 1998 Mar 1;12(5):679-91 PMID: 9499403
  83. Arginine methylation of STAT1: a reassessment.
    Cell. 2004 Nov 24;119(5):587-9; discussion 589-590 PMID: 15550240
  84. Crystal structure of the conserved core of protein arginine methyltransferase PRMT3.
    EMBO J. 2000 Jul 17;19(14):3509-19 PMID: 10899106
  85. The diverse functions of histone lysine methylation.
    Nat Rev Mol Cell Biol. 2005 Nov;6(11):838-49 PMID: 16261189
  86. Tudor domains bind symmetrical dimethylated arginines.
    J Biol Chem. 2005 Aug 5;280(31):28476-83 PMID: 15955813
  87. The structure and oligomerization of the yeast arginine methyltransferase, Hmt1.
    Nat Struct Biol. 2000 Dec;7(12):1165-71 PMID: 11101900
Article Info
Journal
Molecular endocrinology (Baltimore, Md.)
Abbr.
Mol Endocrinol
ISSN
0888-8809
DOI
10.1210/me.2008-0380
Published
2009-04-00
Epub
2009-00-22
Pages
425-33
Language
English
Region
United States
NLM ID
8801431
PMCID
PMC2667706
Subset
IM
Grants
NIDDK NIH HHS · R01 DK055274 · United States
NIDDK NIH HHS · DK55274 · United States
NIDDK NIH HHS · R37 DK055274 · United States
NIDDK NIH HHS · R01 DK043093 · United States
NIDDK NIH HHS · DK43093 · United States
External Links
PubMed source DOI: 10.1210/me.2008-0380 PMC Full Text View journal details
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