Abstract
The basic region-leucine zipper transcription factor c-Jun regulates gene expression and cell function. It participates in the formation of homo- or heterodimeric complexes that specifically bind to DNA sequences called activating protein 1 (AP-1) sites. The stability and activity of c-Jun is regulated by phosphorylation within the N-terminal activation domain. Mitogen- and stress-activated c-Jun N-terminal kinases (JNKs) were previously the only described enzymes phosphorylating c-Jun at the N terminus in vivo. In this report we demonstrate a JNK-independent activation of c-Jun in vivo directed by the constitutive photomorphogenesis (COP9) signalosome. The overexpression of signalosome subunit 2 (Sgn2), a subunit of the COP9 signalosome, leads to de novo assembly of the complex with a partial incorporation of the overexpressed subunit. The de novo formation of COP9 signalosome parallels an increase of c-Jun protein resulting in elevated AP-1 transcriptional activity. The c-Jun activation caused by Sgn2 overexpression is independent of JNK and mitogen-activated protein kinase kinase 4. The data demonstrate the existence of a novel COP9 signalosome-directed c-Jun activation pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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COP9 Signalosome Complex
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / isolation & purification
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DNA-Binding Proteins / metabolism*
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Erythrocytes / metabolism
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GTP-Binding Proteins*
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Genes, Reporter
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HeLa Cells
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Humans
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Intracellular Signaling Peptides and Proteins
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4*
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Mitogen-Activated Protein Kinases / metabolism*
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Molecular Sequence Data
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Peptide Hydrolases
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Phosphorylation
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Protein-Tyrosine Kinases / metabolism
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Proteins / genetics
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Proteins / isolation & purification
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Proteins / metabolism*
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Proto-Oncogene Proteins c-jun / metabolism*
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Recombinant Fusion Proteins / metabolism
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Recombinant Proteins / metabolism
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Repressor Proteins*
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Sequence Deletion
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Transcription Factor AP-1 / metabolism
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Transcription Factors / genetics
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Transcription Factors / isolation & purification
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Transcription Factors / metabolism*
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Transcriptional Activation*
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Transfection
Substances
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COPS2 protein, human
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DNA-Binding Proteins
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GPS1 protein, human
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Intracellular Signaling Peptides and Proteins
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Proteins
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Proto-Oncogene Proteins c-jun
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Recombinant Fusion Proteins
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Recombinant Proteins
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Repressor Proteins
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Transcription Factor AP-1
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Transcription Factors
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Protein-Tyrosine Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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MAP2K4 protein, human
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Mitogen-Activated Protein Kinase Kinases
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Peptide Hydrolases
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COPS5 protein, human
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COP9 Signalosome Complex
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GTP-Binding Proteins