p73 interacts with c-Myc to regulate Y-box-binding protein-1 expression

Hidetaka Uramoto, Hiroto Izumi, Tomoko Ise, Mitsuhiro Tada, Takeshi Uchiumi, Michihiko Kuwano, Kosei Yasumoto, Keiko Funa, Kimitoshi Kohno

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)31694-31702
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number35
DOIs
Publication statusPublished - Aug 30 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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