P079: Loss of DDI2 rewires proteostasis through CCN1-driven compensatory autophagy in cancer
Abstract
The ubiquitin-proteasome system (UPS) primarily targets short-lived and misfolded proteins for degradation by tagging them with polyubiquitin chains and directing them to the proteasome. Many ubiquitinated substrates are shuttled to proteasomes via ubiquitin-binding factors, including DNA-damage inducible 1 homolog 2 (DDI2). When proteasome activity is limited, DDI2 recognizes proteins with elongated ubiquitin chains and facilitates their degradation. DDI2 depletion leads to the accumulation of slowly migrating ubiquitinated proteins, which has been shown to sensitize cancer cells to proteasome inhibition.
Fields of Study & Subjects
Ubiquitin and proteasome pathways
Autophagy in Disease and Therapy
Protein Degradation and Inhibitors
Publication details
- Journal / source
- Genetics in Medicine Open
- Volume
- 4
- Pages
- 103570–103570
- Publication date
- 1 January 2026
- Language
- EN