Abstract
Treatment of cells with pro-inflammatory cytokines or ultraviolet radiation causes activation of the c-Jun NH2-terminal protein kinase (JNK). Activating transcription factor-2 (ATF2) was found to be a target of the JNK signal transduction pathway. ATF2 was phosphorylated by JNK on two closely spaced threonine residues within the NH2-terminal activation domain. The replacement of these phosphorylation sites with alanine inhibited the transcriptional activity of ATF2. These mutations also inhibited ATF2-stimulated gene expression mediated by the retinoblastoma (Rb) tumor suppressor and the adenovirus early region 1A (E1A) oncoprotein. Furthermore, expression of dominant-negative JNK inhibited ATF2 transcriptional activity. Together, these data demonstrate a role for the JNK signal transduction pathway in transcriptional responses mediated by ATF2.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Activating Transcription Factor 2
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Adenovirus E1A Proteins / physiology
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Animals
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Base Sequence
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CHO Cells
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cricetinae
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Cyclic AMP Response Element-Binding Protein / chemistry
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Cyclic AMP Response Element-Binding Protein / genetics
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Cyclic AMP Response Element-Binding Protein / metabolism*
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DNA / metabolism
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Interleukin-1 / pharmacology
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JNK Mitogen-Activated Protein Kinases
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Leucine Zippers*
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Mitogen-Activated Protein Kinases*
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Phosphorylation
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Point Mutation
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Promoter Regions, Genetic
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Retinoblastoma Protein / physiology
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Signal Transduction*
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Transcription Factors*
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Transcription, Genetic*
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Ultraviolet Rays
Substances
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Activating Transcription Factor 2
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Adenovirus E1A Proteins
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Cyclic AMP Response Element-Binding Protein
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Interleukin-1
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Retinoblastoma Protein
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Transcription Factors
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DNA
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases