Functional analysis and intracellular localization of p53 modified by SUMO-1
p53 tumor suppressor is a subject of several post-translational modifications, including phosphorylation, ubiquitination and acetylation, which regulate p53 function. A new covalent modification of p53 at lysine 386 by SUMO-1 was recently identified. To elucidate the function of sumoylated p53, we c...
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| Veröffentlicht in: | Oncogene 2001-05, Vol.20 (20), p.2587-2599 |
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| description | p53 tumor suppressor is a subject of several post-translational modifications, including phosphorylation, ubiquitination and acetylation, which regulate p53 function. A new covalent modification of p53 at lysine 386 by SUMO-1 was recently identified. To elucidate the function of sumoylated p53, we compared the properties of wild type p53 and sumoylation-deficient p53 mutant, K386R. No differences were found between wild type p53 and K386R mutant of p53 in transactivation or growth suppression assays. Moreover, overexpression of SUMO-1 has no effect on p53-regulated transcription. Biochemical fractionation showed that sumoylated p53 is localized in the nucleus and is tightly bound to chromatin structures. p53 and SUMO-1 co-localized in PML nuclear bodies in 293 cells and the nucleoli in MCF7 and HT1080 cells. However, sumoylation-deficient p53 mutant showed a similar pattern of intranuclear localization, suggesting that SUMO-1 does not target p53 to subnuclear structures. These data indicate that SUMO-1 modification of p53 at lysine 386 may not be essential for p53's cellular localization, transcriptional activation, or growth regulation. |
| doi_str_mv | 10.1038/sj.onc.1204362 |
| format | Article |
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Biochemical fractionation showed that sumoylated p53 is localized in the nucleus and is tightly bound to chromatin structures. p53 and SUMO-1 co-localized in PML nuclear bodies in 293 cells and the nucleoli in MCF7 and HT1080 cells. However, sumoylation-deficient p53 mutant showed a similar pattern of intranuclear localization, suggesting that SUMO-1 does not target p53 to subnuclear structures. These data indicate that SUMO-1 modification of p53 at lysine 386 may not be essential for p53's cellular localization, transcriptional activation, or growth regulation.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1204362</identifier><identifier>PMID: 11420669</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing</publisher><subject>Acetylation ; Amino Acid Sequence ; Biological and medical sciences ; Cell Division - physiology ; Cell Nucleus - metabolism ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Chromatin ; Chromatin - metabolism ; DNA Damage ; Enzymes ; Fundamental and applied biological sciences. Psychology ; Humans ; Kinases ; Localization ; Lysine ; lysine 386 ; Molecular and cellular biology ; Mutants ; Nucleoli ; p53 Protein ; Phosphorylation ; Post-translation ; Proteins ; Sequence Homology, Amino Acid ; Sumo ; SUMO protein ; SUMO-1 Protein ; Transcription activation ; Transcriptional Activation ; Transfection ; Tumor Cells, Cultured ; Tumor proteins ; Tumor suppressor genes ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Tumor Suppressor Protein p53 - physiology ; Tumors ; Ubiquitin ; Ubiquitination ; Ubiquitins - biosynthesis ; Ubiquitins - genetics ; Ubiquitins - metabolism</subject><ispartof>Oncogene, 2001-05, Vol.20 (20), p.2587-2599</ispartof><rights>2001 INIST-CNRS</rights><rights>COPYRIGHT 2001 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 3, 2001</rights><rights>Macmillan Publishers Limited 2001.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-9a6f83b356441c91b0b4ca79eb6dc44ba8a3f57afd81763566b889f9d5cc8e213</citedby><cites>FETCH-LOGICAL-c485t-9a6f83b356441c91b0b4ca79eb6dc44ba8a3f57afd81763566b889f9d5cc8e213</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1041007$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11420669$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KWEK, Serena S. S</creatorcontrib><creatorcontrib>DERRY, Jason</creatorcontrib><creatorcontrib>TYNER, Angela L</creatorcontrib><creatorcontrib>ZHIYUAN SHEN</creatorcontrib><creatorcontrib>GUDKOV, Andrei V</creatorcontrib><title>Functional analysis and intracellular localization of p53 modified by SUMO-1</title><title>Oncogene</title><addtitle>Oncogene</addtitle><description>p53 tumor suppressor is a subject of several post-translational modifications, including phosphorylation, ubiquitination and acetylation, which regulate p53 function. A new covalent modification of p53 at lysine 386 by SUMO-1 was recently identified. To elucidate the function of sumoylated p53, we compared the properties of wild type p53 and sumoylation-deficient p53 mutant, K386R. No differences were found between wild type p53 and K386R mutant of p53 in transactivation or growth suppression assays. Moreover, overexpression of SUMO-1 has no effect on p53-regulated transcription. Biochemical fractionation showed that sumoylated p53 is localized in the nucleus and is tightly bound to chromatin structures. p53 and SUMO-1 co-localized in PML nuclear bodies in 293 cells and the nucleoli in MCF7 and HT1080 cells. However, sumoylation-deficient p53 mutant showed a similar pattern of intranuclear localization, suggesting that SUMO-1 does not target p53 to subnuclear structures. These data indicate that SUMO-1 modification of p53 at lysine 386 may not be essential for p53's cellular localization, transcriptional activation, or growth regulation.</description><subject>Acetylation</subject><subject>Amino Acid Sequence</subject><subject>Biological and medical sciences</subject><subject>Cell Division - physiology</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Chromatin</subject><subject>Chromatin - metabolism</subject><subject>DNA Damage</subject><subject>Enzymes</subject><subject>Fundamental and applied biological sciences. 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S</au><au>DERRY, Jason</au><au>TYNER, Angela L</au><au>ZHIYUAN SHEN</au><au>GUDKOV, Andrei V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional analysis and intracellular localization of p53 modified by SUMO-1</atitle><jtitle>Oncogene</jtitle><addtitle>Oncogene</addtitle><date>2001-05-03</date><risdate>2001</risdate><volume>20</volume><issue>20</issue><spage>2587</spage><epage>2599</epage><pages>2587-2599</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>p53 tumor suppressor is a subject of several post-translational modifications, including phosphorylation, ubiquitination and acetylation, which regulate p53 function. A new covalent modification of p53 at lysine 386 by SUMO-1 was recently identified. To elucidate the function of sumoylated p53, we compared the properties of wild type p53 and sumoylation-deficient p53 mutant, K386R. No differences were found between wild type p53 and K386R mutant of p53 in transactivation or growth suppression assays. Moreover, overexpression of SUMO-1 has no effect on p53-regulated transcription. Biochemical fractionation showed that sumoylated p53 is localized in the nucleus and is tightly bound to chromatin structures. p53 and SUMO-1 co-localized in PML nuclear bodies in 293 cells and the nucleoli in MCF7 and HT1080 cells. However, sumoylation-deficient p53 mutant showed a similar pattern of intranuclear localization, suggesting that SUMO-1 does not target p53 to subnuclear structures. These data indicate that SUMO-1 modification of p53 at lysine 386 may not be essential for p53's cellular localization, transcriptional activation, or growth regulation.</abstract><cop>Basingstoke</cop><pub>Nature Publishing</pub><pmid>11420669</pmid><doi>10.1038/sj.onc.1204362</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetylation Amino Acid Sequence Biological and medical sciences Cell Division - physiology Cell Nucleus - metabolism Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Chromatin Chromatin - metabolism DNA Damage Enzymes Fundamental and applied biological sciences. Psychology Humans Kinases Localization Lysine lysine 386 Molecular and cellular biology Mutants Nucleoli p53 Protein Phosphorylation Post-translation Proteins Sequence Homology, Amino Acid Sumo SUMO protein SUMO-1 Protein Transcription activation Transcriptional Activation Transfection Tumor Cells, Cultured Tumor proteins Tumor suppressor genes Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Tumor Suppressor Protein p53 - physiology Tumors Ubiquitin Ubiquitination Ubiquitins - biosynthesis Ubiquitins - genetics Ubiquitins - metabolism |
| title | Functional analysis and intracellular localization of p53 modified by SUMO-1 |
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