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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

Authors

  • Uramoto H
  • Izumi H
  • Ise T
  • Tada M
  • Uchiumi T
  • Kuwano M
  • Yasumoto K
  • Funa K
  • Kohno K

Journal

The Journal of biological chemistry

Publication Data

August 30, 2002

Associated Grants

None

Mesh Terms

  • 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 Suppressor Proteins
  • Y-Box-Binding Protein 1