Abstract
YB-1 is a member of the cold shock domain family of proteins that is important for signaling DNA damage and cell proliferation. YB-1 is induced by DNA damage and can also recognize cisplatin-modified DNA. In this study we observed a 6-fold increase in the steady-state level of YB-1 mRNA in response to cisplatin exposure in cells of the human cancer cell line KB. We present evidence from cotransfection experiments for a critical role of c-Myc and p73 in the transactivation of the YB-1 promoter. p73 transactivated the YB-1 promoter in experiments with Saos-2 cells, which express c-Myc, but not with HO15.19 cells, which lack c-Myc. In turn, c-Myc transactivated an intact YB-1 promoter but not a YB-1 promoter with a mutant E-box, indicating that the E-box is necessary for the response of the promoter to cisplatin. We also found that p73 interacts with c-Myc in vitro and in vivo. Using deletion mutants we showed that the DNA-binding domain of p73 and the C-terminal region of c-Myc are required for the interaction. Furthermore, p73 stimulated the interaction of Max with c-Myc and promoted binding of the c-Myc-Max complex to its target DNA. Our data suggest that p73 stimulates the transcription of the YB-1 promoter by enhancing recruitment of the c-Myc-Max complex to the E-box.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Basic-Leucine Zipper Transcription Factors
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Binding Sites
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Bone Neoplasms
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CCAAT-Enhancer-Binding Proteins / genetics*
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COS Cells
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Chlorocebus aethiops
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Cisplatin / pharmacology
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DNA Damage
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Fibroblasts
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Gene Expression Regulation
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Genes, Tumor Suppressor
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Humans
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KB Cells
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NFI Transcription Factors
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Osteosarcoma
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Promoter Regions, Genetic*
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Proto-Oncogene Proteins c-myc / metabolism*
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RNA, Messenger / genetics
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Rats
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Recombinant Proteins / metabolism
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Sequence Deletion
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription, Genetic / drug effects
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Transcriptional Activation
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Transfection
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Tumor Cells, Cultured
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Tumor Protein p73
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Tumor Suppressor Proteins
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Y-Box-Binding Protein 1
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Basic-Leucine Zipper Transcription Factors
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CCAAT-Enhancer-Binding Proteins
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DNA-Binding Proteins
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MAX protein, human
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Max protein, rat
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Myc associated factor X
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NFI Transcription Factors
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Nuclear Proteins
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Proto-Oncogene Proteins c-myc
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RNA, Messenger
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Recombinant Proteins
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TP73 protein, human
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Transcription Factors
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Tumor Protein p73
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Tumor Suppressor Proteins
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Y-Box-Binding Protein 1
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YBX1 protein, human
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Cisplatin