Methylation of the Retinoblastoma Tumor Suppressor by SMYD2
The retinoblastoma tumor suppressor (RB) is a central cell cycle regulator and tumor suppressor. RB cellular functions are known to be regulated by a diversity of post-translational modifications such as phosphorylation and acetylation, raising the possibility that RB may also be methylated in cells...
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| Veröffentlicht in: | The Journal of biological chemistry 2010-11, Vol.285 (48), p.37733-37740 |
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| container_issue | 48 |
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| container_title | The Journal of biological chemistry |
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| creator | Saddic, Louis A. West, Lisandra E. Aslanian, Aaron Yates, John R. Rubin, Seth M. Gozani, Or Sage, Julien |
| description | The retinoblastoma tumor suppressor (RB) is a central cell cycle regulator and tumor suppressor. RB cellular functions are known to be regulated by a diversity of post-translational modifications such as phosphorylation and acetylation, raising the possibility that RB may also be methylated in cells. Here we demonstrate that RB can be methylated by SMYD2 at lysine 860, a highly conserved and novel site of modification. This methylation event occurs in vitro and in cells, and it is regulated during cell cycle progression, cellular differentiation, and in response to DNA damage. Furthermore, we show that RB monomethylation at lysine 860 provides a direct binding site for the methyl-binding domain of the transcriptional repressor L3MBTL1. These results support the idea that a code of post-translational modifications exists for RB and helps guide its functions in mammalian cells. |
| doi_str_mv | 10.1074/jbc.M110.137612 |
| format | Article |
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RB cellular functions are known to be regulated by a diversity of post-translational modifications such as phosphorylation and acetylation, raising the possibility that RB may also be methylated in cells. Here we demonstrate that RB can be methylated by SMYD2 at lysine 860, a highly conserved and novel site of modification. This methylation event occurs in vitro and in cells, and it is regulated during cell cycle progression, cellular differentiation, and in response to DNA damage. Furthermore, we show that RB monomethylation at lysine 860 provides a direct binding site for the methyl-binding domain of the transcriptional repressor L3MBTL1. These results support the idea that a code of post-translational modifications exists for RB and helps guide its functions in mammalian cells.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M110.137612</identifier><identifier>PMID: 20870719</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Motifs ; Amino Acid Sequence ; Cell Cycle ; Cell Line, Tumor ; Gene Expression Regulation ; Gene Regulation ; Histone-Lysine N-Methyltransferase - genetics ; Histone-Lysine N-Methyltransferase - metabolism ; Humans ; L3MBTL1 ; Methylation ; Molecular Sequence Data ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Post-translational Modification ; Protein Binding ; Protein Methylation ; Retinoblastoma (Rb) ; Retinoblastoma Protein - chemistry ; Retinoblastoma Protein - genetics ; Retinoblastoma Protein - metabolism ; Sequence Alignment ; SMYD2 ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transcription Repressor</subject><ispartof>The Journal of biological chemistry, 2010-11, Vol.285 (48), p.37733-37740</ispartof><rights>2010 © 2010 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2010 by The American Society for Biochemistry and Molecular Biology, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c642t-ac3aee14c9dc18faf7a84b6aa4917e33b5a33300f9fd676ecbde2b8bac6882f43</citedby><cites>FETCH-LOGICAL-c642t-ac3aee14c9dc18faf7a84b6aa4917e33b5a33300f9fd676ecbde2b8bac6882f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988378/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988378/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20870719$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Saddic, Louis A.</creatorcontrib><creatorcontrib>West, Lisandra E.</creatorcontrib><creatorcontrib>Aslanian, Aaron</creatorcontrib><creatorcontrib>Yates, John R.</creatorcontrib><creatorcontrib>Rubin, Seth M.</creatorcontrib><creatorcontrib>Gozani, Or</creatorcontrib><creatorcontrib>Sage, Julien</creatorcontrib><title>Methylation of the Retinoblastoma Tumor Suppressor by SMYD2</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The retinoblastoma tumor suppressor (RB) is a central cell cycle regulator and tumor suppressor. RB cellular functions are known to be regulated by a diversity of post-translational modifications such as phosphorylation and acetylation, raising the possibility that RB may also be methylated in cells. Here we demonstrate that RB can be methylated by SMYD2 at lysine 860, a highly conserved and novel site of modification. This methylation event occurs in vitro and in cells, and it is regulated during cell cycle progression, cellular differentiation, and in response to DNA damage. Furthermore, we show that RB monomethylation at lysine 860 provides a direct binding site for the methyl-binding domain of the transcriptional repressor L3MBTL1. These results support the idea that a code of post-translational modifications exists for RB and helps guide its functions in mammalian cells.</description><subject>Amino Acid Motifs</subject><subject>Amino Acid Sequence</subject><subject>Cell Cycle</subject><subject>Cell Line, Tumor</subject><subject>Gene Expression Regulation</subject><subject>Gene Regulation</subject><subject>Histone-Lysine N-Methyltransferase - genetics</subject><subject>Histone-Lysine N-Methyltransferase - metabolism</subject><subject>Humans</subject><subject>L3MBTL1</subject><subject>Methylation</subject><subject>Molecular Sequence Data</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Post-translational Modification</subject><subject>Protein Binding</subject><subject>Protein Methylation</subject><subject>Retinoblastoma (Rb)</subject><subject>Retinoblastoma Protein - chemistry</subject><subject>Retinoblastoma Protein - genetics</subject><subject>Retinoblastoma Protein - metabolism</subject><subject>Sequence Alignment</subject><subject>SMYD2</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription Repressor</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkVFr1TAYhoMo7ji99k57t6tu-ZK2SRAE2ZwKOww8G-hVSNOvOxltc0zawfn3S-kcejGWmyTkyZs3PIS8B3oMVBQnt7U9XsO846IC9oKsgEqe8xJ-vSQrShnkipXygLyJ8ZamUSh4TQ4YlYIKUCvyaY3jdt-Z0fkh8202bjH7iaMbfN2ZOPreZFdT70O2mXa7gDGmZb3PNuvfZ-wtedWaLuK7h_mQXJ9_vTr9nl9cfvtx-uUit1XBxtxYbhChsKqxIFvTCiOLujImdRHIeV0azjmlrWqbSlRo6wZZLWtjKylZW_BD8nnJ3U11j43FYQym07vgehP22hun_z8Z3Fbf-DvNlJRcyBRw9BAQ_J8J46h7Fy12nRnQT1FLUYCqUonnSa6qRFP6PAkMeCnKmTxZSBt8jAHbx-ZA9WxRJ4t6tqgXi-nGh38__Mj_1ZaAjwvQGq_NTXBRX28YBU5BARRyjlALgUnMncOgo3U4WGxcQDvqxrsnn78HcGa1nQ</recordid><startdate>20101126</startdate><enddate>20101126</enddate><creator>Saddic, Louis A.</creator><creator>West, Lisandra E.</creator><creator>Aslanian, Aaron</creator><creator>Yates, John R.</creator><creator>Rubin, Seth M.</creator><creator>Gozani, Or</creator><creator>Sage, Julien</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TM</scope><scope>7TO</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20101126</creationdate><title>Methylation of the Retinoblastoma Tumor Suppressor by SMYD2</title><author>Saddic, Louis A. ; 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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Amino Acid Motifs Amino Acid Sequence Cell Cycle Cell Line, Tumor Gene Expression Regulation Gene Regulation Histone-Lysine N-Methyltransferase - genetics Histone-Lysine N-Methyltransferase - metabolism Humans L3MBTL1 Methylation Molecular Sequence Data Nuclear Proteins - genetics Nuclear Proteins - metabolism Post-translational Modification Protein Binding Protein Methylation Retinoblastoma (Rb) Retinoblastoma Protein - chemistry Retinoblastoma Protein - genetics Retinoblastoma Protein - metabolism Sequence Alignment SMYD2 Transcription Factors - genetics Transcription Factors - metabolism Transcription Repressor |
| title | Methylation of the Retinoblastoma Tumor Suppressor by SMYD2 |
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