Journal of Biological Chemistry
Volume 277, Issue 35, 30 August 2002, Pages 31694-31702
Journal home page for Journal of Biological Chemistry

GENES: STRUCTURE AND REGULATION
p73 Interacts with c-Myc to Regulate Y-box-binding Protein-1 Expression*

https://doi.org/10.1074/jbc.M200266200Get rights and content
Under a Creative Commons license
open access

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.

Cited by (0)

Published, JBC Papers in Press, June 21, 2002, DOI 10.1074/jbc.M200266200

*

This work was supported in part by a grant-in-aid for Cancer Research from the Ministry of Education, Science, Sports, and Culture of Japan, by Research Grant 99-23106 from the Princess Takamatsu Cancer Research Fund, and by a grant from the Fukuoka Anticancer Research Fund, as well as by grants from the Swedish Cancer Foundation, the Childhood Cancer Foundation, and the Ingabritt and Arne Lundberg Foundation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.