Upregulated PrP^C by HBx enhances NF-κB signal via liquid-liquid phase separation to advance liver cancer.

ABSTRACT: Cellular prion protein (PrP^C) has been implicated in carcinogenic through the activation of various signal pathways, however, the precise mechanisms remain elusive. In vitro studies have shown that PrP^C is prone to undergo liquid-liquid phase separation (LLPS). However, it remains unknown whether PrP^C contributes to LLPS-inducing cancer development. Herein, we observed an upregulation of PrP^C expression in hepatitis B virus-positive hepatocellular carcinoma (HCC). Subsequent investigation revealed that HBx of HBV enhances PrP^C expression in a dose-dependent manner by binding to CREB1. Furthermore, we demonstrated that PrP^C undergoes LLPS and recruits TRAF2/6, TAB2/3, and TAK1 protein, thereby activating the NF-κB signaling p

SUBMITTER: Liu Y 

PROVIDER: S-EPMC11437096 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature