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.
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References
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This is a summary of: Li, Y. et al. Design of PROTACs utilizing the E3 ligase GID4 for targeted protein degradation. Nat. Struct. Mol. Biol. https://doi.org/10.1038/s41594-025-01537-1 (2025).
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Insights into the degradation mechanism of GID4-based proteolysis-targeting chimeras. Nat Struct Mol Biol 32, 1594–1595 (2025). https://doi.org/10.1038/s41594-025-01539-z
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DOI: https://doi.org/10.1038/s41594-025-01539-z
