Transcriptional switch by activating transcription factor 2-derived peptide sensitizes melanoma cells to apoptosis and inhibits their tumorigenicity.
AffiliationRuttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY 10029, USA.
MetadataShow full item record
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.
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.
JournalProceedings of the National Academy of Sciences of the United States of America
- An ATF2-derived peptide sensitizes melanomas to apoptosis and inhibits their growth and metastasis.
- Authors: Bhoumik A, Huang TG, Ivanov V, Gangi L, Qiao RF, Woo SL, Chen SH, Ronai Z
- Issue date: 2002 Sep
- Amino-terminal-derived JNK fragment alters expression and activity of c-Jun, ATF2, and p53 and increases H2O2-induced cell death.
- Authors: Buschmann T, Yin Z, Bhoumik A, Ronai Z
- Issue date: 2000 Jun 2
- The activation of c-Jun NH2-terminal kinase (JNK) by DNA-damaging agents serves to promote drug resistance via activating transcription factor 2 (ATF2)-dependent enhanced DNA repair.
- Authors: Hayakawa J, Depatie C, Ohmichi M, Mercola D
- Issue date: 2003 Jun 6
- c-Jun NH2-terminal kinases target the ubiquitination of their associated transcription factors.
- Authors: Fuchs SY, Xie B, Adler V, Fried VA, Davis RJ, Ronai Z
- Issue date: 1997 Dec 19
- Activating transcription factor 2-derived peptides alter resistance of human tumor cell lines to ultraviolet irradiation and chemical treatment.
- Authors: Bhoumik A, Ivanov V, Ronai Z
- Issue date: 2001 Feb