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Single chain antibody against the common epitope of mutant p53 restores wild-type activity to mutant p53 protein
Here, we describe the biological activity of ME1, a mouse single chain Fv fragment (scFv) against the common epitope of mutant p53, which is efficiently expressed in mammalian cells. We found that in vivo interaction of the conformational p53 mutant R175H protein with the scFv resulted in the acquis...
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| Published in: | FEBS letters 2005-10, Vol.579 (25), p.5609-5615 |
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| Main Authors: | , , , , |
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| cited_by | cdi_FETCH-LOGICAL-c4595-fea74577892b5b11ae0e281e8b973d61014eaae8337a32cb2063dca068c6245b3 |
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| cites | cdi_FETCH-LOGICAL-c4595-fea74577892b5b11ae0e281e8b973d61014eaae8337a32cb2063dca068c6245b3 |
| container_end_page | 5615 |
| container_issue | 25 |
| container_start_page | 5609 |
| container_title | FEBS letters |
| container_volume | 579 |
| creator | Orgad, Sara Goldfinger, Naomi Cohen, Gerald Rotter, Varda Solomon, Beka |
| description | Here, we describe the biological activity of ME1, a mouse single chain Fv fragment (scFv) against the common epitope of mutant p53, which is efficiently expressed in mammalian cells. We found that in vivo interaction of the conformational p53 mutant R175H protein with the scFv resulted in the acquisition of wild-type p53 characteristics, manifested in
trans-activation of p21, as well as induction of apoptosis. Moreover, antibody binding leads to abrogation of the mutant p53 mediated “gain of function” as estimated by downregulation of EGR-1, a transcriptional target of mutant p53. These findings suggest that the scFv restores wild-type properties to mutant p53. |
| doi_str_mv | 10.1016/j.febslet.2005.09.031 |
| format | article |
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trans-activation of p21, as well as induction of apoptosis. Moreover, antibody binding leads to abrogation of the mutant p53 mediated “gain of function” as estimated by downregulation of EGR-1, a transcriptional target of mutant p53. These findings suggest that the scFv restores wild-type properties to mutant p53.</description><identifier>ISSN: 0014-5793</identifier><identifier>EISSN: 1873-3468</identifier><identifier>DOI: 10.1016/j.febslet.2005.09.031</identifier><identifier>PMID: 16213502</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>Activity restoration ; Animals ; Antibodies - genetics ; Antibodies - immunology ; Apoptosis ; Down-Regulation ; Humans ; Immunodominant Epitopes - immunology ; Mice ; Mutation ; p53 ; p53-R175H mutant ; Protein Structure, Tertiary - genetics ; Single chain Fv fragment ; Transcription, Genetic ; Transfection ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - immunology ; Tumor Suppressor Protein p53 - metabolism</subject><ispartof>FEBS letters, 2005-10, Vol.579 (25), p.5609-5615</ispartof><rights>2005</rights><rights>FEBS Letters 579 (2005) 1873-3468 © 2015 Federation of European Biochemical Societies</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4595-fea74577892b5b11ae0e281e8b973d61014eaae8337a32cb2063dca068c6245b3</citedby><cites>FETCH-LOGICAL-c4595-fea74577892b5b11ae0e281e8b973d61014eaae8337a32cb2063dca068c6245b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014579305011415$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3535,27903,27904,45759</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16213502$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Orgad, Sara</creatorcontrib><creatorcontrib>Goldfinger, Naomi</creatorcontrib><creatorcontrib>Cohen, Gerald</creatorcontrib><creatorcontrib>Rotter, Varda</creatorcontrib><creatorcontrib>Solomon, Beka</creatorcontrib><title>Single chain antibody against the common epitope of mutant p53 restores wild-type activity to mutant p53 protein</title><title>FEBS letters</title><addtitle>FEBS Lett</addtitle><description>Here, we describe the biological activity of ME1, a mouse single chain Fv fragment (scFv) against the common epitope of mutant p53, which is efficiently expressed in mammalian cells. We found that in vivo interaction of the conformational p53 mutant R175H protein with the scFv resulted in the acquisition of wild-type p53 characteristics, manifested in
trans-activation of p21, as well as induction of apoptosis. Moreover, antibody binding leads to abrogation of the mutant p53 mediated “gain of function” as estimated by downregulation of EGR-1, a transcriptional target of mutant p53. These findings suggest that the scFv restores wild-type properties to mutant p53.</description><subject>Activity restoration</subject><subject>Animals</subject><subject>Antibodies - genetics</subject><subject>Antibodies - immunology</subject><subject>Apoptosis</subject><subject>Down-Regulation</subject><subject>Humans</subject><subject>Immunodominant Epitopes - immunology</subject><subject>Mice</subject><subject>Mutation</subject><subject>p53</subject><subject>p53-R175H mutant</subject><subject>Protein Structure, Tertiary - genetics</subject><subject>Single chain Fv fragment</subject><subject>Transcription, Genetic</subject><subject>Transfection</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - immunology</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNqNkctu1DAUQC0EokPhE0BesUvqt50VgqqllSqxKKwtx7lpPUriEHta5e9xNCPBrmxsXfnch-9B6CMlNSVUXezrHto0QK4ZIbImTU04fYV21GhecaHMa7QjhIpK6oafoXcp7UmJDW3eojOqGOWSsB2a78P0MAD2jy5M2E05tLFbsXsoYco4P5anOI5xwjCHHGfAscfjIRcSz5LjBVKO5cDPYeiqvBbA-RyeQl5xjv-S8xIzhOk9etO7IcGH032Ofl1f_by8qe5-fL-9_HpXeSEbWfXgtJBam4a1sqXUAQFmKJi20bxTZQUCnAPDuXac-ZYRxTvviDJeMSFbfo4-H-uWvr8PZUo7huRhGNwE8ZCsMqphmsgXQUaENlqIAsoj6JeY0gK9nZcwumW1lNjNid3bkxO7ObGkscVJyft0anBoR-j-Zp0kFODmCJQdwvp_Ve311Td2vwne_BJJKBV0-8yXYykoq30KsNjkA0weurCAz7aL4YVp_wBM3LXT</recordid><startdate>20051024</startdate><enddate>20051024</enddate><creator>Orgad, Sara</creator><creator>Goldfinger, Naomi</creator><creator>Cohen, Gerald</creator><creator>Rotter, Varda</creator><creator>Solomon, Beka</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20051024</creationdate><title>Single chain antibody against the common epitope of mutant p53 restores wild-type activity to mutant p53 protein</title><author>Orgad, Sara ; Goldfinger, Naomi ; Cohen, Gerald ; Rotter, Varda ; Solomon, Beka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4595-fea74577892b5b11ae0e281e8b973d61014eaae8337a32cb2063dca068c6245b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Activity restoration</topic><topic>Animals</topic><topic>Antibodies - genetics</topic><topic>Antibodies - immunology</topic><topic>Apoptosis</topic><topic>Down-Regulation</topic><topic>Humans</topic><topic>Immunodominant Epitopes - immunology</topic><topic>Mice</topic><topic>Mutation</topic><topic>p53</topic><topic>p53-R175H mutant</topic><topic>Protein Structure, Tertiary - genetics</topic><topic>Single chain Fv fragment</topic><topic>Transcription, Genetic</topic><topic>Transfection</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - immunology</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Orgad, Sara</creatorcontrib><creatorcontrib>Goldfinger, Naomi</creatorcontrib><creatorcontrib>Cohen, Gerald</creatorcontrib><creatorcontrib>Rotter, Varda</creatorcontrib><creatorcontrib>Solomon, Beka</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Orgad, Sara</au><au>Goldfinger, Naomi</au><au>Cohen, Gerald</au><au>Rotter, Varda</au><au>Solomon, Beka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Single chain antibody against the common epitope of mutant p53 restores wild-type activity to mutant p53 protein</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>2005-10-24</date><risdate>2005</risdate><volume>579</volume><issue>25</issue><spage>5609</spage><epage>5615</epage><pages>5609-5615</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><abstract>Here, we describe the biological activity of ME1, a mouse single chain Fv fragment (scFv) against the common epitope of mutant p53, which is efficiently expressed in mammalian cells. 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trans-activation of p21, as well as induction of apoptosis. Moreover, antibody binding leads to abrogation of the mutant p53 mediated “gain of function” as estimated by downregulation of EGR-1, a transcriptional target of mutant p53. These findings suggest that the scFv restores wild-type properties to mutant p53.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>16213502</pmid><doi>10.1016/j.febslet.2005.09.031</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0014-5793 |
| ispartof | FEBS letters, 2005-10, Vol.579 (25), p.5609-5615 |
| issn | 0014-5793 1873-3468 |
| language | eng |
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| source | ScienceDirect; Wiley |
| subjects | Activity restoration Animals Antibodies - genetics Antibodies - immunology Apoptosis Down-Regulation Humans Immunodominant Epitopes - immunology Mice Mutation p53 p53-R175H mutant Protein Structure, Tertiary - genetics Single chain Fv fragment Transcription, Genetic Transfection Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - immunology Tumor Suppressor Protein p53 - metabolism |
| title | Single chain antibody against the common epitope of mutant p53 restores wild-type activity to mutant p53 protein |
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