A Global Approach Combining Proteome Analysis and Phenotypic Screening with RNA Interference Yields Novel Apoptosis Regulators
Global approaches like proteome or transcriptome analyses have been performed extensively to identify candidate genes or proteins involved in biological and pathological processes. Here we describe the identification of proteins implicated in the regulation of apoptosis using proteome analysis and t...
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| Veröffentlicht in: | Molecular & cellular proteomics 2005-01, Vol.4 (1), p.44-55 |
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| container_title | Molecular & cellular proteomics |
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| creator | Machuy, Nikolaus Thiede, Bernd Rajalingam, Krishnaraj Dimmler, Christiane Thieck, Oliver Meyer, Thomas F Rudel, Thomas |
| description | Global approaches like proteome or transcriptome analyses have been performed extensively to identify candidate genes or proteins
involved in biological and pathological processes. Here we describe the identification of proteins implicated in the regulation
of apoptosis using proteome analysis and the functional validation of targets by RNA interference. A high-throughput platform
for the validation of synthetic small interfering RNAs (siRNAs) by quantitative real-time PCR was established. Genes of the
identified factors were silenced by automated siRNA transfection, and their role in apoptotic signaling was investigated.
Using this strategy, nine new modulators of apoptosis were identified. A subsequent detailed study demonstrated that hepatoma-derived
growth factor (HDGF) is required for TNFα-induced release of pro-apoptotic factors from mitochondria. The strategy described
here may be used for hypothesis-free, global gene function analysis. |
| doi_str_mv | 10.1074/mcp.M400089-MCP200 |
| format | Article |
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involved in biological and pathological processes. Here we describe the identification of proteins implicated in the regulation
of apoptosis using proteome analysis and the functional validation of targets by RNA interference. A high-throughput platform
for the validation of synthetic small interfering RNAs (siRNAs) by quantitative real-time PCR was established. Genes of the
identified factors were silenced by automated siRNA transfection, and their role in apoptotic signaling was investigated.
Using this strategy, nine new modulators of apoptosis were identified. A subsequent detailed study demonstrated that hepatoma-derived
growth factor (HDGF) is required for TNFα-induced release of pro-apoptotic factors from mitochondria. The strategy described
here may be used for hypothesis-free, global gene function analysis.</description><identifier>ISSN: 1535-9476</identifier><identifier>ISSN: 1535-9484</identifier><identifier>EISSN: 1535-9484</identifier><identifier>DOI: 10.1074/mcp.M400089-MCP200</identifier><identifier>PMID: 15567892</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Apoptosis - physiology ; HeLa Cells ; Humans ; Intercellular Signaling Peptides and Proteins - genetics ; Intercellular Signaling Peptides and Proteins - physiology ; Jurkat Cells ; Mitochondria - metabolism ; Phenotype ; Proteome - analysis ; Proteome - genetics ; Proteome - physiology ; RNA Interference ; RNA, Small Interfering - genetics ; RNA, Small Interfering - pharmacology ; Transcription, Genetic - drug effects ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>Molecular & cellular proteomics, 2005-01, Vol.4 (1), p.44-55</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-da65076bf705e4f104e045438e3932d5d3dc8e2eb9876f614cf7d6f7bcc74cf43</citedby><cites>FETCH-LOGICAL-c399t-da65076bf705e4f104e045438e3932d5d3dc8e2eb9876f614cf7d6f7bcc74cf43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15567892$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Machuy, Nikolaus</creatorcontrib><creatorcontrib>Thiede, Bernd</creatorcontrib><creatorcontrib>Rajalingam, Krishnaraj</creatorcontrib><creatorcontrib>Dimmler, Christiane</creatorcontrib><creatorcontrib>Thieck, Oliver</creatorcontrib><creatorcontrib>Meyer, Thomas F</creatorcontrib><creatorcontrib>Rudel, Thomas</creatorcontrib><title>A Global Approach Combining Proteome Analysis and Phenotypic Screening with RNA Interference Yields Novel Apoptosis Regulators</title><title>Molecular & cellular proteomics</title><addtitle>Mol Cell Proteomics</addtitle><description>Global approaches like proteome or transcriptome analyses have been performed extensively to identify candidate genes or proteins
involved in biological and pathological processes. Here we describe the identification of proteins implicated in the regulation
of apoptosis using proteome analysis and the functional validation of targets by RNA interference. A high-throughput platform
for the validation of synthetic small interfering RNAs (siRNAs) by quantitative real-time PCR was established. Genes of the
identified factors were silenced by automated siRNA transfection, and their role in apoptotic signaling was investigated.
Using this strategy, nine new modulators of apoptosis were identified. A subsequent detailed study demonstrated that hepatoma-derived
growth factor (HDGF) is required for TNFα-induced release of pro-apoptotic factors from mitochondria. The strategy described
here may be used for hypothesis-free, global gene function analysis.</description><subject>Apoptosis - physiology</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Intercellular Signaling Peptides and Proteins - genetics</subject><subject>Intercellular Signaling Peptides and Proteins - physiology</subject><subject>Jurkat Cells</subject><subject>Mitochondria - metabolism</subject><subject>Phenotype</subject><subject>Proteome - analysis</subject><subject>Proteome - genetics</subject><subject>Proteome - physiology</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>Transcription, Genetic - drug effects</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>1535-9476</issn><issn>1535-9484</issn><issn>1535-9484</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMlOwzAQhi0EYim8AAfkE7eAnXhJjlHFJrFULAdOluNMGqMkDnYK6oVnJ6UVPc0cvv8fzYfQKSUXlEh22Zr-4oERQtIsepjOYkJ20CHlCY8ylrLd_12KA3QUwgchMaGS76MDyrmQaRYfop8c3zSu0A3O-947bWo8dW1hO9vN8cy7AVwLOO90sww2YN2VeFZD54Zlbw1-MR7gD_22Q42fH3N81w3gK_DQGcDvFpoy4Ef3BasDrh_cquUZ5otGD86HY7RX6SbAyWZO0Nv11ev0Nrp_urmb5veRSbJsiEotOJGiqCThwCpKGBDGWZJCkiVxycukNCnEUGSpFJWgzFSyFJUsjJHjzpIJOl_3jj9-LiAMqrXBQNPoDtwiKCqlZIKLEYzXoPEuBA-V6r1ttV8qStTKuhqtq411tbY-hs427YuihXIb2WjeArWd19_WgyqsMzW0iimqGEt-AV4Piy0</recordid><startdate>20050101</startdate><enddate>20050101</enddate><creator>Machuy, Nikolaus</creator><creator>Thiede, Bernd</creator><creator>Rajalingam, Krishnaraj</creator><creator>Dimmler, Christiane</creator><creator>Thieck, Oliver</creator><creator>Meyer, Thomas F</creator><creator>Rudel, Thomas</creator><general>American Society for Biochemistry and Molecular Biology</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>7TM</scope></search><sort><creationdate>20050101</creationdate><title>A Global Approach Combining Proteome Analysis and Phenotypic Screening with RNA Interference Yields Novel Apoptosis Regulators</title><author>Machuy, Nikolaus ; Thiede, Bernd ; Rajalingam, Krishnaraj ; Dimmler, Christiane ; Thieck, Oliver ; Meyer, Thomas F ; Rudel, Thomas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-da65076bf705e4f104e045438e3932d5d3dc8e2eb9876f614cf7d6f7bcc74cf43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Apoptosis - physiology</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Intercellular Signaling Peptides and Proteins - genetics</topic><topic>Intercellular Signaling Peptides and Proteins - physiology</topic><topic>Jurkat Cells</topic><topic>Mitochondria - metabolism</topic><topic>Phenotype</topic><topic>Proteome - analysis</topic><topic>Proteome - genetics</topic><topic>Proteome - physiology</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>Transcription, Genetic - drug effects</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Machuy, Nikolaus</creatorcontrib><creatorcontrib>Thiede, Bernd</creatorcontrib><creatorcontrib>Rajalingam, Krishnaraj</creatorcontrib><creatorcontrib>Dimmler, Christiane</creatorcontrib><creatorcontrib>Thieck, Oliver</creatorcontrib><creatorcontrib>Meyer, Thomas F</creatorcontrib><creatorcontrib>Rudel, Thomas</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><jtitle>Molecular & cellular proteomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Machuy, Nikolaus</au><au>Thiede, Bernd</au><au>Rajalingam, Krishnaraj</au><au>Dimmler, Christiane</au><au>Thieck, Oliver</au><au>Meyer, Thomas F</au><au>Rudel, Thomas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Global Approach Combining Proteome Analysis and Phenotypic Screening with RNA Interference Yields Novel Apoptosis Regulators</atitle><jtitle>Molecular & cellular proteomics</jtitle><addtitle>Mol Cell Proteomics</addtitle><date>2005-01-01</date><risdate>2005</risdate><volume>4</volume><issue>1</issue><spage>44</spage><epage>55</epage><pages>44-55</pages><issn>1535-9476</issn><issn>1535-9484</issn><eissn>1535-9484</eissn><abstract>Global approaches like proteome or transcriptome analyses have been performed extensively to identify candidate genes or proteins
involved in biological and pathological processes. Here we describe the identification of proteins implicated in the regulation
of apoptosis using proteome analysis and the functional validation of targets by RNA interference. A high-throughput platform
for the validation of synthetic small interfering RNAs (siRNAs) by quantitative real-time PCR was established. Genes of the
identified factors were silenced by automated siRNA transfection, and their role in apoptotic signaling was investigated.
Using this strategy, nine new modulators of apoptosis were identified. A subsequent detailed study demonstrated that hepatoma-derived
growth factor (HDGF) is required for TNFα-induced release of pro-apoptotic factors from mitochondria. The strategy described
here may be used for hypothesis-free, global gene function analysis.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>15567892</pmid><doi>10.1074/mcp.M400089-MCP200</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Apoptosis - physiology HeLa Cells Humans Intercellular Signaling Peptides and Proteins - genetics Intercellular Signaling Peptides and Proteins - physiology Jurkat Cells Mitochondria - metabolism Phenotype Proteome - analysis Proteome - genetics Proteome - physiology RNA Interference RNA, Small Interfering - genetics RNA, Small Interfering - pharmacology Transcription, Genetic - drug effects Tumor Necrosis Factor-alpha - metabolism |
| title | A Global Approach Combining Proteome Analysis and Phenotypic Screening with RNA Interference Yields Novel Apoptosis Regulators |
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