Dissection of Melanogenesis with Small Molecules Identifies Prohibitin as a Regulator
Bioactive compounds can be used to selectively modulate gene function. We utilized a chemical genetic approach to dissect the mammalian pigmentation pathway and identify protein regulators. We screened a tagged library of 1170 small molecules in a cell-based assay and discovered a class of pigment-e...
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| Veröffentlicht in: | Chemistry & biology 2005-04, Vol.12 (4), p.477-484 |
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| container_title | Chemistry & biology |
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| creator | Snyder, Jane R. Hall, Andrea Ni-Komatsu, Li Khersonsky, Sonya M. Chang, Young-Tae Orlow, Seth J. |
| description | Bioactive compounds can be used to selectively modulate gene function. We utilized a chemical genetic approach to dissect the mammalian pigmentation pathway and identify protein regulators. We screened a tagged library of 1170 small molecules in a cell-based assay and discovered a class of pigment-enhancing chemicals. From this class we characterized the small molecule melanogenin. Using melanogenin bound to an affinity matrix and amino acid sequencing, we identified the mitochondrial protein, prohibitin, as an intracellular binding target. Studies employing siRNA demonstrate that prohibitin is required for melanogenin to exert its propigmentary effects and reveal an unsuspected functional role for this protein in melanin induction. This represents a mechanism by which propigmentary signals are transduced and ultimately provides a potential target for the treatment of pigmentary disorders. |
| doi_str_mv | 10.1016/j.chembiol.2005.02.014 |
| format | Article |
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We utilized a chemical genetic approach to dissect the mammalian pigmentation pathway and identify protein regulators. We screened a tagged library of 1170 small molecules in a cell-based assay and discovered a class of pigment-enhancing chemicals. From this class we characterized the small molecule melanogenin. Using melanogenin bound to an affinity matrix and amino acid sequencing, we identified the mitochondrial protein, prohibitin, as an intracellular binding target. Studies employing siRNA demonstrate that prohibitin is required for melanogenin to exert its propigmentary effects and reveal an unsuspected functional role for this protein in melanin induction. This represents a mechanism by which propigmentary signals are transduced and ultimately provides a potential target for the treatment of pigmentary disorders.</description><identifier>ISSN: 1074-5521</identifier><identifier>EISSN: 1879-1301</identifier><identifier>DOI: 10.1016/j.chembiol.2005.02.014</identifier><identifier>PMID: 15850985</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>Amino Acid Sequence ; Blotting, Western ; Cells, Cultured ; Chromatography, Affinity ; Drug Evaluation, Preclinical ; Electrophoresis, Polyacrylamide Gel ; Fluorescent Antibody Technique ; Humans ; Melanins - biosynthesis ; Melanocytes - drug effects ; Melanocytes - metabolism ; Molecular Sequence Data ; Monophenol Monooxygenase - metabolism ; Pigmentation - physiology ; Protein Binding ; Repressor Proteins - physiology ; RNA, Small Interfering - metabolism ; Signal Transduction - physiology ; Triazines - metabolism ; Triazines - pharmacology</subject><ispartof>Chemistry & biology, 2005-04, Vol.12 (4), p.477-484</ispartof><rights>2005 Elsevier Ltd</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c414t-5823ab81202eda085e27e150e66ca1399bd472b1498073d41121822ac39c88c53</citedby><cites>FETCH-LOGICAL-c414t-5823ab81202eda085e27e150e66ca1399bd472b1498073d41121822ac39c88c53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1074552105000736$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15850985$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Snyder, Jane R.</creatorcontrib><creatorcontrib>Hall, Andrea</creatorcontrib><creatorcontrib>Ni-Komatsu, Li</creatorcontrib><creatorcontrib>Khersonsky, Sonya M.</creatorcontrib><creatorcontrib>Chang, Young-Tae</creatorcontrib><creatorcontrib>Orlow, Seth J.</creatorcontrib><title>Dissection of Melanogenesis with Small Molecules Identifies Prohibitin as a Regulator</title><title>Chemistry & biology</title><addtitle>Chem Biol</addtitle><description>Bioactive compounds can be used to selectively modulate gene function. We utilized a chemical genetic approach to dissect the mammalian pigmentation pathway and identify protein regulators. We screened a tagged library of 1170 small molecules in a cell-based assay and discovered a class of pigment-enhancing chemicals. From this class we characterized the small molecule melanogenin. Using melanogenin bound to an affinity matrix and amino acid sequencing, we identified the mitochondrial protein, prohibitin, as an intracellular binding target. Studies employing siRNA demonstrate that prohibitin is required for melanogenin to exert its propigmentary effects and reveal an unsuspected functional role for this protein in melanin induction. This represents a mechanism by which propigmentary signals are transduced and ultimately provides a potential target for the treatment of pigmentary disorders.</description><subject>Amino Acid Sequence</subject><subject>Blotting, Western</subject><subject>Cells, Cultured</subject><subject>Chromatography, Affinity</subject><subject>Drug Evaluation, Preclinical</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Fluorescent Antibody Technique</subject><subject>Humans</subject><subject>Melanins - biosynthesis</subject><subject>Melanocytes - drug effects</subject><subject>Melanocytes - metabolism</subject><subject>Molecular Sequence Data</subject><subject>Monophenol Monooxygenase - metabolism</subject><subject>Pigmentation - physiology</subject><subject>Protein Binding</subject><subject>Repressor Proteins - physiology</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Signal Transduction - physiology</subject><subject>Triazines - metabolism</subject><subject>Triazines - pharmacology</subject><issn>1074-5521</issn><issn>1879-1301</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEFP3DAQha0K1IVt_wLyiVvCjBMnzq0V0HYlUBEtZ8txZne9cmKwk1b992S1W3HkNO_w3jy9j7ELhBwBq6tdbrfUty74XADIHEQOWH5gZ6jqJsMC8GTWUJeZlAIX7DylHQCgaqqPbIFSSWiUPGNPNy4lsqMLAw9rfk_eDGFDAyWX-F83bvmv3njP74MnO3lKfNXRMLq1m-VDDFvXutEN3CRu-CNtJm_GED-x07XxiT4f75I9fbv9ff0ju_v5fXX99S6zJZZjJpUoTKtQgKDOgJIkakIJVFXWYNE0bVfWosWyUVAXXYkoUAlhbNFYpawsluzy8Pc5hpeJ0qh7lyz5eQSFKemqruumqvbG6mC0MaQUaa2fo-tN_KcR9B6o3un_QPUeqAahZ6Bz8OLYMLU9dW-xI8HZ8OVgoHnnH0dRJ-tosNS5OHPVXXDvdbwCBqmJ2Q</recordid><startdate>20050401</startdate><enddate>20050401</enddate><creator>Snyder, Jane R.</creator><creator>Hall, Andrea</creator><creator>Ni-Komatsu, Li</creator><creator>Khersonsky, Sonya M.</creator><creator>Chang, Young-Tae</creator><creator>Orlow, Seth J.</creator><general>Elsevier Ltd</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>7X8</scope></search><sort><creationdate>20050401</creationdate><title>Dissection of Melanogenesis with Small Molecules Identifies Prohibitin as a Regulator</title><author>Snyder, Jane R. ; 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| ispartof | Chemistry & biology, 2005-04, Vol.12 (4), p.477-484 |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Free Full-Text Journals in Chemistry |
| subjects | Amino Acid Sequence Blotting, Western Cells, Cultured Chromatography, Affinity Drug Evaluation, Preclinical Electrophoresis, Polyacrylamide Gel Fluorescent Antibody Technique Humans Melanins - biosynthesis Melanocytes - drug effects Melanocytes - metabolism Molecular Sequence Data Monophenol Monooxygenase - metabolism Pigmentation - physiology Protein Binding Repressor Proteins - physiology RNA, Small Interfering - metabolism Signal Transduction - physiology Triazines - metabolism Triazines - pharmacology |
| title | Dissection of Melanogenesis with Small Molecules Identifies Prohibitin as a Regulator |
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