Oncolytic Newcastle disease virus promotes tumor cell apoptosis through SUMO-1-dependent PRKN-mediated degradation of c-Myc

NDV infection reduces c-Myc protein levels in tumor cells in a time- and dose-dependent manner, and c-Myc knockdown further enhances NDV-induced intrinsic apoptosis.

• Why it matters: c-Myc is widely upregulated in cancers, but direct targeting is difficult; understanding how oncolytic NDV disrupts oncogenic signaling could improve antitumor strategies.
• What they did: NDV promotes ubiquitin-proteasome-dependent c-Myc degradation via ubiquitination at Lys142, with PRKN identified as the key E3 ligase and SUMO-1 driving PRKN nuclear translocation.
• The result: SUMO-1 or PRKN knockdown impairs PRKN nuclear accumulation, restores c-Myc stability, and attenuates NDV-induced apoptosis; c-Myc K142R or c-Myc restoration protects tumor cells, while NDV suppresses tumor growth in an A549 xenograft model.