Insights into the degradation mechanism of GID4-based proteolysis-targeting chimeras

Abstract

The Pro/N-degron E3 ligase GID4 can be harnessed for proteolysis-targeting chimera (PROTAC) applications, as demonstrated by a GID4-based bromodomain-containing protein 4 (BRD4)-targeting PROTAC, which inhibits cell proliferation and exhibits antitumor activity. Structural analysis of the GID4–PROTAC–BRD4 ternary complexes reveals plasticity in the underlying interactions, providing valuable insights into the degradation mechanism.