Bee Hui Liu, Miao Liu, Sridhar Radhakrishnan, Chaitanya Kumar Jaladanki, Chong Gao, Jing Ping Tang, Kalpana Kumari, Mei Lin Go, Kim Anh L Vu, Hyuk-Soo Seo, Kijun Song, Xi Tian, Li Feng, Justin L Tan, Mahmoud A Bassal, Haribabu Arthanari, Jun Qi, Sirano Dhe-Paganon, Hao Fan, Daniel G Tenen, Li Chai
Immunomodulatory imide drugs (IMiDs) degrade specific C2H2 zinc finger degrons in transcription factors, making them effective against certain cancers. SALL4, a cancer driver, contains seven C2H2 zinc fingers in four clusters, including an IMiD degron in zinc finger cluster two (ZFC2). Surprisingly, IMiDs do not inhibit growth of SALL4 expressing cancer cells. To overcome this limit, we focused on a non-IMiD degron, SALL4 zinc finger cluster four (ZFC4). By combining AlphaFold and the ZFC4-DNA crystal structure, we identified a potential ZFC4 drug pocket...
January 3, 2024: bioRxiv