p73 Interacts with c-Myc to regulate Y-box-binding protein-1 expression.
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.
Pubmed ID: 12080043 RIS Download
Animals | Basic Helix-Loop-Helix Leucine Zipper Transcription Factors | Basic-Leucine Zipper Transcription Factors | Binding Sites | Bone Neoplasms | CCAAT-Enhancer-Binding Proteins | COS Cells | Cercopithecus aethiops | Cisplatin | DNA Damage | DNA-Binding Proteins | Fibroblasts | Gene Expression Regulation | Genes, Tumor Suppressor | Humans | KB Cells | NFI Transcription Factors | Nuclear Proteins | Osteosarcoma | Promoter Regions, Genetic | Proto-Oncogene Proteins c-myc | RNA, Messenger | Rats | Recombinant Proteins | Sequence Deletion | Transcription Factors | Transcription, Genetic | Transcriptional Activation | Transfection | Tumor Cells, Cultured | Tumor Protein p73 | Tumor Suppressor Proteins | Y-Box-Binding Protein 1