Transcriptional switch by activating transcription factor 2-derived peptide sensitizes melanoma cells to apoptosis and inhibits their tumorigenicity.

2.50
Hdl Handle:
http://hdl.handle.net/10541/78514
Title:
Transcriptional switch by activating transcription factor 2-derived peptide sensitizes melanoma cells to apoptosis and inhibits their tumorigenicity.
Authors:
Bhoumik, Anindita; Jones, Nic; Ronai, Ze'ev
Abstract:
The 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.
Affiliation:
Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY 10029, USA.
Citation:
Transcriptional 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.
Journal:
Proceedings of the National Academy of Sciences of the United States of America
Issue Date:
23-Mar-2004
URI:
http://hdl.handle.net/10541/78514
DOI:
10.1073/pnas.0400195101
PubMed ID:
15010535
Type:
Article
Language:
en
ISSN:
0027-8424
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
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.en
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
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