LEF1 enhances β-catenin transactivation through IDR-dependent liquid–liquid phase separation
Bing Zhao, Zhuoxin Li, Shaoqing Yu, Tingting Li, Wen Wang, Ran Liu, Biyu Zhang, Xiya Fang, Yezhuang Shen, Qiuying Han, Xin Xu, Kai Wang, Weili Gong, Tao Li, Ailing Li, Tao Zhou, Weihua Li, Teng Li- Health, Toxicology and Mutagenesis
- Plant Science
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- Ecology
Wnt/β-catenin signaling plays a crucial role in cancer development, primarily activated by β-catenin forming a transcription complex with LEF/TCF in the nucleus and initiating the transcription of Wnt target genes. Here, we report that LEF1, a member of the LEF/TCF family, can form intrinsically disordered region (IDR)-dependent condensates with β-catenin both in vivo and in vitro, which is required for β-catenin-dependent transcription. Notably, LEF1 with disrupted IDR lost its promoting activity on tumor proliferation and metastasis, which can be restored by substituting with FUS IDR. Our findings provide new insight into the essential role of liquid–liquid phase separation in Wnt/β-catenin signaling and present a potential new target for cancer therapy.