Protein methylation: a signal event in post-translational modification

Aletta, John M.; Cimato, Thomas R.; Ettinger, Murray J.

doi:10.1016/s0968-0004(98)01185-2

Cited by 155 publications

(110 citation statements)

References 24 publications

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“…Since methylation does not change the overall charge on lysine and arginine residues, the addition of methyl groups is unlikely to cause a significant global structural change within the protein substrate. 288 Instead, the methyl groups could block biomolecular interactions by rendering steric hindrance on Lys and Arg residues, or in the opposite manner, provide an epitopic motif for introducing physical interaction with downstream effector proteins. Excitingly, several protein domains, such as Tudor domain, Chromo domain and PWWP domain, 289,290291,292 have been identified to recognize specific methyl marks, which suggests that protein methylation could be extensively involved in mediating intra-and intermolecular protein-protein or proteinnucleic acid interactions and cell signaling.…”

Section: Discussionmentioning

confidence: 99%

Chemical and biochemical approaches in the study of histone methylation and demethylation

Luo

Wang

et al. 2010

Med. Res. Rev.

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Histone methylation represents one of the most critical epigenetic events in DNA function regulation in eukaryotic organisms. Classic molecular biology and genetics tools provide significant knowledge about mechanisms and physiological roles of histone methyltransferases and demethylases in various cellular processes. In addition to this stream line, development and application of chemistry and chemistry-related techniques are increasingly involved in biological study, and provide information otherwise difficulty to obtain by standard molecular biology methods. Herein, we review recent achievements and progress in developing and applying chemical and biochemical approaches in the study of histone methylation, including chromatin immunoprecipitation (ChIP), chemical ligation, mass spectrometry (MS), biochemical assays, and inhibitor development. These technological advances allow histone methylation to be studied from genome-wide level to molecular and atomic levels. With ChIP technology, information can be obtained about precise mapping of histone methylation patterns at specific promoters, genes or other genomic regions. MS is particularly useful in detecting and analyzing methylation marks in histone and nonhistone protein substrates. Chemical approaches that permit site-specific incorporation of methyl groups into histone proteins greatly facilitate the investigation of the biological impacts of methylation at individual modification sites. Discovery and design of selective organic inhibitors of histone methyltransferases and demethylases provide chemical probes to interrogate methylation-mediated cellular pathways. Overall, these chemistry-related technological advances have greatly improved our understanding of the biological functions of histone methylation in normal physiology and diseased states, and also are of great potential to translate basic epigenetics research into diagnostic and therapeutic application in the clinic.

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Section: Discussionmentioning

confidence: 99%

Chemical and biochemical approaches in the study of histone methylation and demethylation

Luo

Wang

et al. 2010

Med. Res. Rev.

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“…Proteins can be methylated on lysine, arginine, histidine, or carboxyl residues (Aletta et al, 1998). In addition, when some aspartate residues in proteins spontaneously convert to isoaspartate as a result of protein aging, a methylation mechanism is used in cells to reverse this process (Najbauer et al, 1996).…”

Section: Types Of Protein Methylation and Their Possible Roles In Varmentioning

confidence: 99%

“…In addition, when some aspartate residues in proteins spontaneously convert to isoaspartate as a result of protein aging, a methylation mechanism is used in cells to reverse this process (Najbauer et al, 1996). Speci®c roles for carboxy-methylation of proteins such as Ras and protein phosphatase 2A have been identi®ed in various signaling pathways, and recent evidence has implicated arginine-speci®c protein methyltransferases in several signaling pathways, although in most of these cases the speci®c roles of protein methylation and the relevant protein substrates have not been identi®ed (Aletta et al, 1998;Gary and Clarke, 1998;Lin et al, 1996;Abramovitch et al, 1997). Arginine methylation is important for nuclear export of some hnRNP proteins (Shen et al, 1998;Nichols et al, 2000;Gary and Clarke, 1998).…”

Section: Types Of Protein Methylation and Their Possible Roles In Varmentioning

confidence: 99%

“…Arginine methylation occurs on either or both of the two terminal guanidino nitrogen atoms, resulting in three possible products: monomethylarginine; N G ,N Gdimethylarginine, in which both methyl groups are on the same nitrogen (asymmetric dimethylarginine); and N G ,N' G -dimethylarginine, in which each nitrogen atom receives one methyl group (symmetric dimethylarginine) (Aletta et al, 1998;Gary and Clarke, 1998). cDNA clones for ®ve genetically distinct but related mammalian arginine methyltransferases have been isolated: PRMT1 , PRMT2/ HRMT1L1 (Scott et al, 1998), PRMT3 (Tang et al, 1998), CARM1 (Chen et al, 1999a), and JBP1 (Pollack et al, 1999).…”

Section: Families Of Lysine and Arginine-speci®c Protein Methyltransfmentioning

confidence: 99%

“…In fact, PRMT1 and the yeast Hmt1/RMT1 can methylate many RNA binding proteins which are known to be involved in various aspects of RNA processing, transport, translation, and metabolism (Najbauer et al, 1993;Lin et al, 1996;Gary and Clarke, 1998;Aletta et al, 1998;Shen et al, 1998;Smith et al, 1999;Tang et al, 2000b;Nichols et al, 2000). The fact that transcriptional initiation and many post-transcriptional steps are known to be coupled and coordinated (Monsalve et al, 2000) suggests that some proteins currently classi®ed as transcriptional coactivators could actually function by facilitating post-transcriptional steps.…”

Section: Methylation Of Non-histone Substratesmentioning

confidence: 99%

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Role of protein methylation in chromatin remodeling and transcriptional regulation

2001

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Recent ®ndings suggest that lysine and arginine-speci®c methylation of histones may cooperate with other types of post-translational histone modi®cation to regulate chromatin structure and gene transcription. Proteins that methylate histones on arginine residues can collaborate with other coactivators to enhance the activity of speci®c transcriptional activators such as nuclear receptors. Lysine methylation of histones is associated with transcriptionally active nuclei, regulates other types of histone modi®ca-tions, and is necessary for proper mitotic cell divisions. The fact that some transcription factors and proteins involved in RNA processing can also be methylated suggests that protein methylation may also contribute in other ways to regulation of transcription and post-transcriptional steps in gene regulation. In future work, it will be important to develop methods for evaluating the precise roles of protein methylation in the regulation of native genes in physiological settings, e.g. by using chromatin immunoprecipitation assays, di erentiating cell culture systems, and genetically altered cells and animals. It will also be important to isolate additional protein methyltransferases by molecular cloning and to characterize new methyltransferase substrates, the regulation of methyltransferase activities, and the roles of new methyltransferases and substrates. Oncogene (2001) 20, 3014 ± 3020.

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BTG gene expression in the p53-dependent and -independent cellular response to DNA damage

et al. 2000

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Exposure of mammalian cells to genotoxic agents evokes a complex cellular response. An ordered series of molecular events is necessary to sense DNA damage, transduce the signal, and ultimately delay the cell cycle or trigger apoptosis. Recently, we have shown that BTG2/TIS21 gene expression was induced in response to DNA damage through a p53-dependent pathway. This gene belongs to a newly identified family of structurally related genes whose other known human members are BTG1, BTG3, and Tob. To define the respective involvement of these four related genes in the cellular response to DNA damage, we studied their expression in human cell lines after a variety of genotoxic treatments. Our results demonstrated that were BTG1, BTG2/TIS21, and Tob genes the DNA damage--inducible genes. However, BTG2/TIS21 appeared to be the only p53-transcriptional target gene. We speculate that BTG proteins may play a coordinate role in a general transduction pathway that is induced in response to DNA damage. It has been previously described that recombinant BTG1 and BTG2/TIS21 can physically interact with PRMT1, an arginine methyl transferase, suggesting that BTG1 and BTG2/TIS21 induction may lead to posttranslational modifications of cellular proteins. In support of this hypothesis, we showed that the endogenous induction of BTG1 and BTG2 after genotoxic treatment was correlated with a modulation of protein methylation.

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Protein methylation: a signal event in post-translational modification

Cited by 155 publications

References 24 publications

Chemical and biochemical approaches in the study of histone methylation and demethylation

Chemical and biochemical approaches in the study of histone methylation and demethylation

Role of protein methylation in chromatin remodeling and transcriptional regulation

BTG gene expression in the p53-dependent and -independent cellular response to DNA damage

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