Apoptosis induced in mammalian cells by small peptides that functionally antagonize the Rb-regulated E2F transcription factor
A variety of studies implicate the E2F transcription factor as a critical regulator of the mammalian cell cycle. The E2F pathway is aberrant in most, if not all, human tumor cells; therefore, therapeutic regimes that modulate E2F activity may provide an approach for reinstating growth control in sit...
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Veröffentlicht in: | Nature biotechnology 1997-09, Vol.15 (9), p.896-901 |
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description | A variety of studies implicate the E2F transcription factor as a critical regulator of the mammalian cell cycle. The E2F pathway is aberrant in most, if not all, human tumor cells; therefore, therapeutic regimes that modulate E2F activity may provide an approach for reinstating growth control in situations where normal physiological control is lost. To elucidate the role of E2F in the cell cycle and assess its value as a therapeutic target, we have introduced peptides that functionally antagonize E2F DNA binding activity into mammalian cells. Introduction of these peptides into mammalian tumor cells caused the rapid onset of apoptosis, an outcome that correlates with the inactivation of physiological E2F. |
doi_str_mv | 10.1038/nbt0997-896 |
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La</creator><creatorcontrib>Bandara, Lasantha R. ; Girling, Rowena ; Thangue, Nicholas B. La</creatorcontrib><description>A variety of studies implicate the E2F transcription factor as a critical regulator of the mammalian cell cycle. The E2F pathway is aberrant in most, if not all, human tumor cells; therefore, therapeutic regimes that modulate E2F activity may provide an approach for reinstating growth control in situations where normal physiological control is lost. To elucidate the role of E2F in the cell cycle and assess its value as a therapeutic target, we have introduced peptides that functionally antagonize E2F DNA binding activity into mammalian cells. Introduction of these peptides into mammalian tumor cells caused the rapid onset of apoptosis, an outcome that correlates with the inactivation of physiological E2F.</description><identifier>ISSN: 1087-0156</identifier><identifier>EISSN: 1546-1696</identifier><identifier>DOI: 10.1038/nbt0997-896</identifier><identifier>PMID: 9306407</identifier><identifier>CODEN: NABIF9</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Ageing, cell death ; Agriculture ; Amino Acid Sequence ; Animals ; Apoptosis - drug effects ; Apoptosis - genetics ; Bioinformatics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedical Engineering/Biotechnology ; Biomedicine ; Biotechnology ; Carrier Proteins ; Cell Cycle Proteins - antagonists & inhibitors ; Cell Cycle Proteins - genetics ; Cell physiology ; Dimerization ; DNA-Binding Proteins - antagonists & inhibitors ; DNA-Binding Proteins - genetics ; E2F Transcription Factors ; Fundamental and applied biological sciences. Psychology ; Humans ; Life Sciences ; Mammals ; Molecular and cellular biology ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Peptides - pharmacology ; Promoter Regions, Genetic - genetics ; Protein Biosynthesis - drug effects ; Protein Biosynthesis - genetics ; research-article ; Retinoblastoma-Binding Protein 1 ; Transcription Factor DP1 ; Transcription Factors - antagonists & inhibitors ; Transcription Factors - genetics ; Transcription Factors - physiology ; Transfection ; Tumor Cells, Cultured</subject><ispartof>Nature biotechnology, 1997-09, Vol.15 (9), p.896-901</ispartof><rights>Nature Publishing Company 1997</rights><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c350t-4bed990d54afb16cc2f69a2ac2ce6f0970495a83e1e6058a954610aa64d4db023</citedby><cites>FETCH-LOGICAL-c350t-4bed990d54afb16cc2f69a2ac2ce6f0970495a83e1e6058a954610aa64d4db023</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nbt0997-896$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nbt0997-896$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2815096$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9306407$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bandara, Lasantha R.</creatorcontrib><creatorcontrib>Girling, Rowena</creatorcontrib><creatorcontrib>Thangue, Nicholas B. La</creatorcontrib><title>Apoptosis induced in mammalian cells by small peptides that functionally antagonize the Rb-regulated E2F transcription factor</title><title>Nature biotechnology</title><addtitle>Nat Biotechnol</addtitle><addtitle>Nat Biotechnol</addtitle><description>A variety of studies implicate the E2F transcription factor as a critical regulator of the mammalian cell cycle. The E2F pathway is aberrant in most, if not all, human tumor cells; therefore, therapeutic regimes that modulate E2F activity may provide an approach for reinstating growth control in situations where normal physiological control is lost. To elucidate the role of E2F in the cell cycle and assess its value as a therapeutic target, we have introduced peptides that functionally antagonize E2F DNA binding activity into mammalian cells. Introduction of these peptides into mammalian tumor cells caused the rapid onset of apoptosis, an outcome that correlates with the inactivation of physiological E2F.</description><subject>Ageing, cell death</subject><subject>Agriculture</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - genetics</subject><subject>Bioinformatics</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering/Biotechnology</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Carrier Proteins</subject><subject>Cell Cycle Proteins - antagonists & inhibitors</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell physiology</subject><subject>Dimerization</subject><subject>DNA-Binding Proteins - antagonists & inhibitors</subject><subject>DNA-Binding Proteins - genetics</subject><subject>E2F Transcription Factors</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Mammals</subject><subject>Molecular and cellular biology</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Site-Directed</subject><subject>Peptides - pharmacology</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Protein Biosynthesis - drug effects</subject><subject>Protein Biosynthesis - genetics</subject><subject>research-article</subject><subject>Retinoblastoma-Binding Protein 1</subject><subject>Transcription Factor DP1</subject><subject>Transcription Factors - antagonists & inhibitors</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - physiology</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><issn>1087-0156</issn><issn>1546-1696</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1v1DAQhi0EKm3hxBnJB8QFAuN8eONjVbUFqRISgnM0cSaLq8QOHuewSP3veNmoJ04z8vv4tfwI8UbBJwVV-9n3CYzZFa3Rz8S5ampdKG3087xDuytANfqluGB-AABda30mzkyVN9idi8erJSwpsGPp_LBaGvKUM84zTg69tDRNLPuD5HwwyYWW5AZimX5hkuPqbXLB5-Qg0SfcB-_-UA5Jfu-LSPt1wpQrb8pbmSJ6ttEtxxtyRJtCfCVejDgxvd7mpfh5e_Pj-ktx_-3u6_XVfWGrBlJR9zQYA0NT49grbW05aoMl2tKSHsHsoDYNthUp0tC0aLICBYi6Huqhh7K6FO9PvUsMv1fi1M2Oj19DT2HlTmnQYMoj-OEE2hiYI43dEt2M8dAp6I6yu012l2Vn-u1Wu_YzDU_sZjfn77Yc2eI0ZgPW8RNWtqqBfzUfTxjnxO8pdg9hjdkq__fVv0OfmDA</recordid><startdate>19970901</startdate><enddate>19970901</enddate><creator>Bandara, Lasantha R.</creator><creator>Girling, Rowena</creator><creator>Thangue, Nicholas B. La</creator><general>Nature Publishing Group US</general><general>Nature</general><scope>IQODW</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>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>19970901</creationdate><title>Apoptosis induced in mammalian cells by small peptides that functionally antagonize the Rb-regulated E2F transcription factor</title><author>Bandara, Lasantha R. ; Girling, Rowena ; Thangue, Nicholas B. La</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c350t-4bed990d54afb16cc2f69a2ac2ce6f0970495a83e1e6058a954610aa64d4db023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Ageing, cell death</topic><topic>Agriculture</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - genetics</topic><topic>Bioinformatics</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering/Biotechnology</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Carrier Proteins</topic><topic>Cell Cycle Proteins - antagonists & inhibitors</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell physiology</topic><topic>Dimerization</topic><topic>DNA-Binding Proteins - antagonists & inhibitors</topic><topic>DNA-Binding Proteins - genetics</topic><topic>E2F Transcription Factors</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Mammals</topic><topic>Molecular and cellular biology</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Site-Directed</topic><topic>Peptides - pharmacology</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Protein Biosynthesis - drug effects</topic><topic>Protein Biosynthesis - genetics</topic><topic>research-article</topic><topic>Retinoblastoma-Binding Protein 1</topic><topic>Transcription Factor DP1</topic><topic>Transcription Factors - antagonists & inhibitors</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - physiology</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bandara, Lasantha R.</creatorcontrib><creatorcontrib>Girling, Rowena</creatorcontrib><creatorcontrib>Thangue, Nicholas B. 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subjects | Ageing, cell death Agriculture Amino Acid Sequence Animals Apoptosis - drug effects Apoptosis - genetics Bioinformatics Biological and medical sciences Biomedical and Life Sciences Biomedical Engineering/Biotechnology Biomedicine Biotechnology Carrier Proteins Cell Cycle Proteins - antagonists & inhibitors Cell Cycle Proteins - genetics Cell physiology Dimerization DNA-Binding Proteins - antagonists & inhibitors DNA-Binding Proteins - genetics E2F Transcription Factors Fundamental and applied biological sciences. Psychology Humans Life Sciences Mammals Molecular and cellular biology Molecular Sequence Data Mutagenesis, Site-Directed Peptides - pharmacology Promoter Regions, Genetic - genetics Protein Biosynthesis - drug effects Protein Biosynthesis - genetics research-article Retinoblastoma-Binding Protein 1 Transcription Factor DP1 Transcription Factors - antagonists & inhibitors Transcription Factors - genetics Transcription Factors - physiology Transfection Tumor Cells, Cultured |
title | Apoptosis induced in mammalian cells by small peptides that functionally antagonize the Rb-regulated E2F transcription factor |
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