Targeted protein degradation is a promising drug discovery approach. A study now describes transferrin receptor targeting chimeras (TransTACS), which lysosomally degrade membrane proteins with potent specificity and efficacy. TransTACs reversibly regulate the tumor-killing activity of CAR-T cells and inhibit drug-resistant EGFR-driven cancers in mice.
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References
Eldeeb, M. A., Zorca, C. E. & Goiran, T. Commun. Chem. 3, 149 (2020).
Tsai, J. M., Nowak, R. P., Ebert, B. L. & Fischer, E. S. Nat. Rev. Mol. Cell Biol. 25, 740–757 (2024).
Wu, T. et al. Nat. Struct. Mol. Biol. 27, 605–614 (2020).
Nalawansha, D. A. & Crews, C. M. Cell Chem. Biol. 27, 998–1014 (2020).
Alabi, S. B. & Crews, C. M. J. Biol. Chem. 296, 100647 (2021).
Banik, S. M. et al. Nature 584, 291–297 (2020).
Zhang, D. et al. Nature https://doi.org/10.1038/s41586-024-07947-3 (2024).
Su, L.-Y. et al. Cell Chem. Biol. 31, 1219–1230.e5 (2024).
Serrano, I. Nat. Chem. Biol. 20, 1387 (2024).
Uslu, U. & June, C. H. Nat. Biotechnol. https://doi.org/10.1038/s41587-024-02446-2 (2024).
Schett, G. et al. Nat. Rev. Rheumatol. 20, 531–544 (2024).
Chung, J. B., Brudno, J. N., Borie, D. & Kochenderfer, J. N. Nat. Rev. Immunol. 24, 830–845 (2024).
Abramson, J. et al. Nature 630, 493–500 (2024).
Huang, B. et al. Nature https://doi.org/10.1038/s41586-024-07948-2 (2024).
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Hohman, G., Shahid, M. & Eldeeb, M. Targeted degradation of membrane proteins. Nat Struct Mol Biol 32, 2–4 (2025). https://doi.org/10.1038/s41594-024-01461-w
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DOI: https://doi.org/10.1038/s41594-024-01461-w
