Working model of RNF214 functions in HCC. Source: Lin et al., 2024. “The RNF214-TEAD-YAP signaling axis promotes hepatocellular carcinoma progression via TEAD ubiquitylation”, Nat Commun 15, 4995 (2024).

RNF214 is a poorly characterized RING finger-containing ubiquitin ligase. In a new study, its role in regulating the Hippo signaling pathway and hepatocellular carcinoma (HCC) development was investigated.

Lin et al. discovered that RNF214 ubiquitylates TEAD transcription factors at their C-terminal YAP binding domains without affecting protein stability or localization. Rather, RNF214 increase interactions between TEADs and YAP/TAZ, increasing the expression of Hippo target genes.

The study employed various techniques, including APEX proximity labeling coupled with mass spectrometry, to identify RNF214 interacting proteins. Results showed that RNF214 is overexpressed in HCC and promotes HCC tumorigenesis via the Hippo pathway.

The researchers demonstrated that RNF214 knockdown or knockout inhibits HCC cell proliferation, migration, and tumor growth. They also found that RNF214 overexpression positively correlates with poor prognosis in HCC patients.

This study uncovers a critical mechanism regulating the downstream transcription network of the Hippo pathway through a novel RNF214-TEAD-YAP signaling axis. The findings suggest that RNF214 could be a potential therapeutic target for HCC treatment.

The study utilized an IonOpticks Aurora Ultimate 25×75 C18 UHPLC column for peptide separation in the mass spectrometry analysis, contributing to the high-quality proteomic data obtained.

Publication
Nature Communications

Authors

Mengjia Lin, Xiaoyun Zheng, Jianing Yan, Fei Huang, Yilin Chen, Ran Ding, Jinkai Wan, Lei Zhang, Chenliang Wang, Jinchang Pan, Xiaolei Cao, Kaiyi Fu, Yan Lou, Xin-Hua Feng, Junfang Ji, Bin Zhao, Fei Lan, Li Shen, Xianglei He, Yunqing Qiu, Jianping Jin

Title

The RNF214-TEAD-YAP signaling axis promotes hepatocellular carcinoma progression via TEAD ubiquitylation