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dc.contributor.authorBhoumik, Anindita
dc.contributor.authorJones, Nic
dc.contributor.authorRonai, Ze'ev
dc.date.accessioned2009-08-25T14:13:42Z
dc.date.available2009-08-25T14:13:42Z
dc.date.issued2004-03-23
dc.identifier.citationTranscriptional switch by activating transcription factor 2-derived peptide sensitizes melanoma cells to apoptosis and inhibits their tumorigenicity. 2004, 101 (12):4222-7 Proc. Natl. Acad. Sci. U.S.A.en
dc.identifier.issn0027-8424
dc.identifier.pmid15010535
dc.identifier.doi10.1073/pnas.0400195101
dc.identifier.urihttp://hdl.handle.net/10541/78514
dc.description.abstractThe notorious resistance of melanoma cells to drug treatment can be overcome by expression of a 50-aa peptide derived from activating transcription factor 2 (ATF2(50-100)). Here we demonstrate that ATF2(50-100) induced apoptosis by sequestering ATF2 to the cytoplasm, thereby inhibiting its transcriptional activities. Furthermore, ATF2(50-100) binds to c-Jun N-terminal kinase (JNK) and increases its activity. Mutation within ATF2(50-100) that impairs association with JNK and the inhibition of JNK or c-Jun expression by RNA interference (RNAi) reduces the degree of ATF2(50-100)-induced apoptosis. In contrast, TAM67, a dominant negative of the Jun family of transcription factors, or JunD RNAi attenuates sensitization of melanoma cells expressing ATF2(50-100) to apoptosis after treatment with anisomycin, which is used as a model drug. Mutations within the JNK binding region of ATF2(50-100) or expression of TAM67 or JunD RNAi attenuates inhibition of melanoma's tumorigenicity by ATF2(50-100). We conclude that inhibition of ATF2 in concert with increased JNK/Jun and JunD activities is central for the sensitization of melanoma cells to apoptosis and inhibition of their tumorigenicity.
dc.language.isoenen
dc.subject.meshActivating Transcription Factor 2
dc.subject.meshAnimals
dc.subject.meshApoptosis
dc.subject.meshCyclic AMP Response Element-Binding Protein
dc.subject.meshCytoplasm
dc.subject.meshHumans
dc.subject.meshJNK Mitogen-Activated Protein Kinases
dc.subject.meshMelanoma
dc.subject.meshMice
dc.subject.meshMitogen-Activated Protein Kinases
dc.subject.meshMutation
dc.subject.meshPeptides
dc.subject.meshProto-Oncogene Proteins c-jun
dc.subject.meshTranscription Factors
dc.titleTranscriptional switch by activating transcription factor 2-derived peptide sensitizes melanoma cells to apoptosis and inhibits their tumorigenicity.en
dc.typeArticleen
dc.contributor.departmentRuttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY 10029, USA.en
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen
html.description.abstractThe notorious resistance of melanoma cells to drug treatment can be overcome by expression of a 50-aa peptide derived from activating transcription factor 2 (ATF2(50-100)). Here we demonstrate that ATF2(50-100) induced apoptosis by sequestering ATF2 to the cytoplasm, thereby inhibiting its transcriptional activities. Furthermore, ATF2(50-100) binds to c-Jun N-terminal kinase (JNK) and increases its activity. Mutation within ATF2(50-100) that impairs association with JNK and the inhibition of JNK or c-Jun expression by RNA interference (RNAi) reduces the degree of ATF2(50-100)-induced apoptosis. In contrast, TAM67, a dominant negative of the Jun family of transcription factors, or JunD RNAi attenuates sensitization of melanoma cells expressing ATF2(50-100) to apoptosis after treatment with anisomycin, which is used as a model drug. Mutations within the JNK binding region of ATF2(50-100) or expression of TAM67 or JunD RNAi attenuates inhibition of melanoma's tumorigenicity by ATF2(50-100). We conclude that inhibition of ATF2 in concert with increased JNK/Jun and JunD activities is central for the sensitization of melanoma cells to apoptosis and inhibition of their tumorigenicity.


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