Abstract
Upon a certain DNA damage including cisplatin treatment, p73 is stabilized and exerts its growth-suppressive and/or proapoptotic function. However, the precise molecular basis by which the intracellular levels of p73 are regulated remains unclear. In the present study, we have identified RanBPM as a novel binding partner of p73α by yeast-based two-hybrid screening, and also found that RanBPM has an ability to stabilize p73α. GST pull-down assays and co-immunoprecipitation experiments revealed that RanBPM directly bound to the extreme COOH-terminal region of p73α, whereas it failed to interact with p53. Co-expression of RanBPM with p73α resulted in the nuclear translocation of RanBPM, and both proteins co-localized in cell nucleus as examined by indirect immunofluorescent staining. It is worth noting that the expression of RanBPM inhibited the ubiquitination of p73α, and thereby prolonged its half-life. Subsequent studies demonstrated that the proapoptotic activity of p73α was significantly enhanced in the presence of RanBPM. Taken together, our present findings implicate a novel role for RanBPM in the regulation of p73 stability and function.
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Acknowledgements
We are grateful to Dr S Sakiyama for helpful discussion. This work was supported in part by a Grant-in-Aid from the Ministry of Health and Welfare for a New 10-Year Strategy for Cancer Control, a Grant-in-Aid for Scientific Research on Priority Areas, a Grant-in-Aid for Scientific Research (B) from the Ministry of Education, Science, Sports and Culture, Japan, and a found from the Hisamitsu Pharmaceutical Company.
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Kramer, S., Ozaki, T., Miyazaki, K. et al. Protein stability and function of p73 are modulated by a physical interaction with RanBPM in mammalian cultured cells. Oncogene 24, 938–944 (2005). https://doi.org/10.1038/sj.onc.1208257
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DOI: https://doi.org/10.1038/sj.onc.1208257
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