Jian Zhu¹, Karin Dahlman-wright¹, Staffan Stromblad¹, Cecilia Williams² Philip Jonsson³, Ting Zhuang³, Chunyan Zhao¹

¹Bioscience and nutrition, Karolinska Institutet, ²Science for Llife Laboratory, ³Department of Biology and Chemistry, University of Houston

Objective:To investigate the role of RNF31 in relation to P53 signaling and proliferation in breast cancer. Method: Western blot, q-pcr, immune precipitation, flow cytometry, cell culture, microarray data analysis. Result: We used an unbiased approach to identify signal pathways that are regulated by RNF31 in breast cancer cells revealing P53 signaling as a potential target of RNF31. We report that depletion of RNF31 in breast cancer cells causes cell cycle arrest and induces apoptosis an effect that is reversed by depletion of P53.Additionally, we demonstrate that RNF31 decreases the stability of P53 in breast cancer cells. Furthermore, we show that RNF31 can interact with theP53/MDM2 complex and facilitate P53 poly-ubiquitination and degradation by stabilizing the E3 ubiquiting ligase MDM2 suggesting a molecular mechanism by which RNF31 regulates cell death. Analysis of publically available clinical datasets shows that RNF31 expression negatively correlates with expression ofP53 target genes, including IGFBP3 and BTG1 consistent with RNF31 regulatingP53 function also in vivo. Conclusion: our findings indicate that RNF31 could be a potential therapeutic target to restore P53 function in breast cancer.

Key Words: breast cancer RNF31  P53