Characterization of two peptide epitopes on Mdm2 oncoprotein that affect p53 degradation
Phosphorylation of Mdm2, in response to DNA damage, resulted in prevention of p53 degradation in the cytoplasm as well as reduction of its binding with monoclonal antibody (mAb) 2A10. Using a 15-mer phage-peptide library, we identified two 2A10-epitopes on human Mdm2 (hdm2): at positions 255–266 (LD...
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| Veröffentlicht in: | Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2002-10, Vol.23 (10), p.1719-1725 |
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| container_title | Peptides (New York, N.Y. : 1980) |
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| creator | Balass, M. Kalef, E. Maya, R. Wilder, S. Oren, M. Katchalski-Katzir, E. |
| description | Phosphorylation of Mdm2, in response to DNA damage, resulted in prevention of p53 degradation in the cytoplasm as well as reduction of its binding with monoclonal antibody (mAb) 2A10. Using a 15-mer phage-peptide library, we identified two 2A10-epitopes on human Mdm2 (hdm2): at positions 255–266 (LDSEDYSLSEEG) and 389–400 (QESDDYSQPSTS). Synthetic peptides corresponding to the above sites, inhibit the binding of mAb2A10 to Mdm2 with high (4.5×10
−9
M) and moderate affinity (1.1×10
−7
M), respectively. Phospho-derivatives of these peptides, and of single human Mdm2 mutations S260D or S395D resulted in a considerable reduction in their binding with mAb2A10. These results provide a molecular explanation for the observation that reactivity of Mdm2 with mAb2A10 is inhibited by phosphorylation. |
| doi_str_mv | 10.1016/S0196-9781(02)00147-X |
| format | Article |
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−9
M) and moderate affinity (1.1×10
−7
M), respectively. Phospho-derivatives of these peptides, and of single human Mdm2 mutations S260D or S395D resulted in a considerable reduction in their binding with mAb2A10. These results provide a molecular explanation for the observation that reactivity of Mdm2 with mAb2A10 is inhibited by phosphorylation.</description><identifier>ISSN: 0196-9781</identifier><identifier>EISSN: 1873-5169</identifier><identifier>DOI: 10.1016/S0196-9781(02)00147-X</identifier><identifier>PMID: 12383858</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Anti-Mdm2 mAb2A10 ; Antibodies, Monoclonal - isolation & purification ; Antibodies, Monoclonal - metabolism ; Antibodies, Monoclonal - pharmacology ; Binding Sites ; Epitope Mapping ; Epitopes ; Escherichia coli - genetics ; Glutathione Transferase - metabolism ; Humans ; Mutation ; Peptide epitopes ; Peptide Fragments - chemistry ; Peptide Fragments - genetics ; Peptide Fragments - immunology ; Peptide Fragments - metabolism ; Peptides - chemistry ; Phage-peptide library ; Phospho-peptides ; Phosphorylation ; Protein Binding ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins - immunology ; Proto-Oncogene Proteins - metabolism ; Recombinant Proteins - metabolism ; Serine - metabolism ; Tumor Suppressor Protein p53 - metabolism ; Tyrosine - metabolism</subject><ispartof>Peptides (New York, N.Y. : 1980), 2002-10, Vol.23 (10), p.1719-1725</ispartof><rights>2002 Elsevier Science Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c361t-29aee8353bd228cd97fd844d3fc00dae5abf44295dc2ca8e3cc78cdcf2de6cbc3</citedby><cites>FETCH-LOGICAL-c361t-29aee8353bd228cd97fd844d3fc00dae5abf44295dc2ca8e3cc78cdcf2de6cbc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S019697810200147X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12383858$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Balass, M.</creatorcontrib><creatorcontrib>Kalef, E.</creatorcontrib><creatorcontrib>Maya, R.</creatorcontrib><creatorcontrib>Wilder, S.</creatorcontrib><creatorcontrib>Oren, M.</creatorcontrib><creatorcontrib>Katchalski-Katzir, E.</creatorcontrib><title>Characterization of two peptide epitopes on Mdm2 oncoprotein that affect p53 degradation</title><title>Peptides (New York, N.Y. : 1980)</title><addtitle>Peptides</addtitle><description>Phosphorylation of Mdm2, in response to DNA damage, resulted in prevention of p53 degradation in the cytoplasm as well as reduction of its binding with monoclonal antibody (mAb) 2A10. Using a 15-mer phage-peptide library, we identified two 2A10-epitopes on human Mdm2 (hdm2): at positions 255–266 (LDSEDYSLSEEG) and 389–400 (QESDDYSQPSTS). Synthetic peptides corresponding to the above sites, inhibit the binding of mAb2A10 to Mdm2 with high (4.5×10
−9
M) and moderate affinity (1.1×10
−7
M), respectively. Phospho-derivatives of these peptides, and of single human Mdm2 mutations S260D or S395D resulted in a considerable reduction in their binding with mAb2A10. These results provide a molecular explanation for the observation that reactivity of Mdm2 with mAb2A10 is inhibited by phosphorylation.</description><subject>Anti-Mdm2 mAb2A10</subject><subject>Antibodies, Monoclonal - isolation & purification</subject><subject>Antibodies, Monoclonal - metabolism</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Binding Sites</subject><subject>Epitope Mapping</subject><subject>Epitopes</subject><subject>Escherichia coli - genetics</subject><subject>Glutathione Transferase - metabolism</subject><subject>Humans</subject><subject>Mutation</subject><subject>Peptide epitopes</subject><subject>Peptide Fragments - chemistry</subject><subject>Peptide Fragments - genetics</subject><subject>Peptide Fragments - immunology</subject><subject>Peptide Fragments - metabolism</subject><subject>Peptides - chemistry</subject><subject>Phage-peptide library</subject><subject>Phospho-peptides</subject><subject>Phosphorylation</subject><subject>Protein Binding</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins - immunology</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Recombinant Proteins - metabolism</subject><subject>Serine - metabolism</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tyrosine - metabolism</subject><issn>0196-9781</issn><issn>1873-5169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtPWzEQRq2KCgLlJxR5hcrigh_3Ya8QivpAAnXRVsrOcsZjMErii-20or8ek0SwZDWLOd88DiGfOTvnjPcXvxjXfaMHxb8wccYYb4dm9oFMuBpk0_Fe75HJK3JADnN-YIy1rVb75IALqaTq1ITMpvc2WSiYwn9bQlzR6Gn5F-mIYwkOKY6hxBEzra1btxS1QhxTLBhWtNzbQq33CIWOnaQO75J1mzmfyEdvFxmPd_WI_Pn29ff0R3Pz8_v19OqmAdnz0ghtEZXs5NwJocDpwTvVtk56YMxZ7Ozct63QnQMBVqEEGCoGXjjsYQ7yiJxu59abHteYi1mGDLhY2BXGdTaD4EozrSvYbUFIMeeE3owpLG16MpyZF6Vmo9S8-DJMmI1SM6u5k92C9XyJ7i21c1iByy2A9c2_AZPJEHAF6EKqYoyL4Z0Vz3GsiKc</recordid><startdate>20021001</startdate><enddate>20021001</enddate><creator>Balass, M.</creator><creator>Kalef, E.</creator><creator>Maya, R.</creator><creator>Wilder, S.</creator><creator>Oren, M.</creator><creator>Katchalski-Katzir, E.</creator><general>Elsevier Inc</general><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></search><sort><creationdate>20021001</creationdate><title>Characterization of two peptide epitopes on Mdm2 oncoprotein that affect p53 degradation</title><author>Balass, M. ; Kalef, E. ; Maya, R. ; Wilder, S. ; Oren, M. ; Katchalski-Katzir, E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c361t-29aee8353bd228cd97fd844d3fc00dae5abf44295dc2ca8e3cc78cdcf2de6cbc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Anti-Mdm2 mAb2A10</topic><topic>Antibodies, Monoclonal - isolation & purification</topic><topic>Antibodies, Monoclonal - metabolism</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Binding Sites</topic><topic>Epitope Mapping</topic><topic>Epitopes</topic><topic>Escherichia coli - genetics</topic><topic>Glutathione Transferase - metabolism</topic><topic>Humans</topic><topic>Mutation</topic><topic>Peptide epitopes</topic><topic>Peptide Fragments - chemistry</topic><topic>Peptide Fragments - genetics</topic><topic>Peptide Fragments - immunology</topic><topic>Peptide Fragments - metabolism</topic><topic>Peptides - chemistry</topic><topic>Phage-peptide library</topic><topic>Phospho-peptides</topic><topic>Phosphorylation</topic><topic>Protein Binding</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins - immunology</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Recombinant Proteins - metabolism</topic><topic>Serine - metabolism</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Tyrosine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Balass, M.</creatorcontrib><creatorcontrib>Kalef, E.</creatorcontrib><creatorcontrib>Maya, R.</creatorcontrib><creatorcontrib>Wilder, S.</creatorcontrib><creatorcontrib>Oren, M.</creatorcontrib><creatorcontrib>Katchalski-Katzir, E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Peptides (New York, N.Y. : 1980)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Balass, M.</au><au>Kalef, E.</au><au>Maya, R.</au><au>Wilder, S.</au><au>Oren, M.</au><au>Katchalski-Katzir, E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of two peptide epitopes on Mdm2 oncoprotein that affect p53 degradation</atitle><jtitle>Peptides (New York, N.Y. : 1980)</jtitle><addtitle>Peptides</addtitle><date>2002-10-01</date><risdate>2002</risdate><volume>23</volume><issue>10</issue><spage>1719</spage><epage>1725</epage><pages>1719-1725</pages><issn>0196-9781</issn><eissn>1873-5169</eissn><abstract>Phosphorylation of Mdm2, in response to DNA damage, resulted in prevention of p53 degradation in the cytoplasm as well as reduction of its binding with monoclonal antibody (mAb) 2A10. Using a 15-mer phage-peptide library, we identified two 2A10-epitopes on human Mdm2 (hdm2): at positions 255–266 (LDSEDYSLSEEG) and 389–400 (QESDDYSQPSTS). Synthetic peptides corresponding to the above sites, inhibit the binding of mAb2A10 to Mdm2 with high (4.5×10
−9
M) and moderate affinity (1.1×10
−7
M), respectively. Phospho-derivatives of these peptides, and of single human Mdm2 mutations S260D or S395D resulted in a considerable reduction in their binding with mAb2A10. These results provide a molecular explanation for the observation that reactivity of Mdm2 with mAb2A10 is inhibited by phosphorylation.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12383858</pmid><doi>10.1016/S0196-9781(02)00147-X</doi><tpages>7</tpages></addata></record> |
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| issn | 0196-9781 1873-5169 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Anti-Mdm2 mAb2A10 Antibodies, Monoclonal - isolation & purification Antibodies, Monoclonal - metabolism Antibodies, Monoclonal - pharmacology Binding Sites Epitope Mapping Epitopes Escherichia coli - genetics Glutathione Transferase - metabolism Humans Mutation Peptide epitopes Peptide Fragments - chemistry Peptide Fragments - genetics Peptide Fragments - immunology Peptide Fragments - metabolism Peptides - chemistry Phage-peptide library Phospho-peptides Phosphorylation Protein Binding Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - immunology Proto-Oncogene Proteins - metabolism Recombinant Proteins - metabolism Serine - metabolism Tumor Suppressor Protein p53 - metabolism Tyrosine - metabolism |
| title | Characterization of two peptide epitopes on Mdm2 oncoprotein that affect p53 degradation |
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