Blocking PPARγ interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression
Pengbo Yang, Pei-pei Hou, Fuyuan Liu, Wenbin Hong, Hang‐zi Chen, Xiaoyu Sun, Li Peng, Yi Zhang, Cui-yu Ju, Lijuan Luo, Sheng-fu Wu, Jia-xin Zhou, Zhijing Wang, Jianping He, Li Li, Tong‐Jin Zhao, Xianming Deng, Tianwei Lin, Qiao Wu
Abstract
to suppress their transcriptions, which hampered the fatty acid uptake, leading to the inhibition of cell proliferation. Peroxisome proliferator-activated receptor-γ (PPARγ) played an antagonistic role in this process through binding to Nur77 to facilitate ubiquitin ligase Trim13-mediated ubiquitination and degradation of Nur77. Cocrystallographic and functional analysis revealed that Csn-B, a Nur77-targeting compound, promoted the formation of Nur77 homodimer to prevent PPARγ binding by steric hindrance, thereby strengthening the Nur77's inhibitory role in breast cancer. Therefore, our study reveals a regulatory function of Nur77 in breast cancer via impeding fatty acid uptake.