Transcription factor Y-box binding protein 1 binds preferentially to cisplatin-modified DNA and interacts with proliferating cell nuclear antigen

Ise Tomoko, Gunji Nagatani, Toshihiro Imamura, Ken Kato, Hiroshi Takano, Minoru Nomoto, Hiroto Izumi, Haruki Ohmori, Tatsuro Okamoto, Takefumi Ohga, Takeshi Uchiumi, Michihiko Kuwano, Kimitoshi Kohno

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Abstract

The Y-box binding protein (YB-1) binds to inverted CCAAT box sequences that are present in the promoter region of many genes. We previously showed that YB-1 is overexpressed in human cancer cell lines that are resistant to cisplatin and that the depletion of YB-1 by transfection of a vector expressing YB-1 antisense RNA increases the sensitivity of human cancer cells to cisplatin. To determine whether YB-1 can bind to cisplatin-modified DNA, we fused YB-1 cDNA to glutathione S-transferase (GST) cDNA and purified the resulting GST fusion protein. When we tested the fusion protein with unmodified or cisplatin-modified oligonucleotides, we found that GST-YB-1 bound more strongly to cisplatin-modified oligonucleotides, as did GST fusion proteins of high mobility group 1 (HMG1), HMG2, and xeroderma pigmentosum group A protein. When we assayed the ability of proliferating cell nuclear antigen (PCNA) to interact with the GST fusion proteins, we observed binding to YB-1 but not to HMG1, HMG2, or xeroderma pigmentosum group A. Subsequent experiments demonstrated that YB-1 and PCNA interact directly via the COOH- terminal region of YB-1. Using immunochemical coprecipitation methods, we observed binding of YB-1 and PCNA in vivo. These results suggest that YB-1 can function as a recognition protein for cisplatin-damaged DNA and that it may be important in DNA repair or in directing the cellular response to DNA damage.

Original languageEnglish
Pages (from-to)342-346
Number of pages5
JournalCancer Research
Volume59
Issue number2
Publication statusPublished - Jan 16 1999

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Tomoko, I., Nagatani, G., Imamura, T., Kato, K., Takano, H., Nomoto, M., ... Kohno, K. (1999). Transcription factor Y-box binding protein 1 binds preferentially to cisplatin-modified DNA and interacts with proliferating cell nuclear antigen. Cancer Research, 59(2), 342-346.