The oncolytic avian reovirus p17 protein triggers chaperone-mediated autophagy by modulating Hsp90 and the T-complex protein-1 ring complex chaperones and co-chaperones to activate the IKK/NF-κB signaling.

ABSTRACT: This study is the first to reveal that oncolytic avian reovirus (ARV) modulates the IKK/NF-κB signaling through the Hsp90-Cdc37, T-complex protein-1 ring complex (TRiC)/Hsc70, and TRiC-phosducin-like protein 1 (PhLP1) chaperone complexes, thereby inducing chaperone-mediated autophagy in mammalian and human cancer lines (referred to as Vero and A549). Specifically, the ARV p17 protein elevates the binding of co-chaperone PhLP1 to TRiC, thereby reducing the complex formation of TRiC-Hsc70 and leading to IκB degradation, suggesting that these two co-chaperones exhibit a competitive relationship. The p17 protein of ARV plays a crucial role in enhancing the formation of the TRiC/PhLP1 complex to protect viral proteins from ubiquitin-proteasome-mediated degradation. Interestingly, we found that

SUBMITTER: Huang W 

PROVIDER: S-EPMC12724251 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature