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PROTEIN DEGRADATION

TAGing for destruction

Nature Chemical Biology volume 14, pages 414–415 (2018)Cite this article

Proteins brought to an E3 ubiquitin ligase are polyubiquitylated for rapid degradation via the proteasome. A new study developed a tag-based degradation system using heterobifunctional degradation inducers called dTAGs, which rapidly depleted FKBP12F36V-fused proteins in cultured cells and in mice.

Specific depletion or functional perturbation of a protein of interest (POI) is important for understanding its function and for drug discovery. Expression control systems working at the protein level are drawing more attention primarily because depletion of POIs is much quicker than in other systems functioning at the DNA or mRNA level (for example, siRNA), such that one can observe an immediate and direct consequence after protein depletion, before the phenotype is compromised or complicated by secondary effects. Reversibility and tunability are additional advantages of the expression control systems working at the protein level. Existing approaches are used mainly in cell culture, and only a few have been tested in mice. A new study by Nabet et al.1 showed that proteins fused with FKBP12F36V, a mutant of the 12-kDa FK506-binding protein (FKBP12), can be rapidly degraded in cultured cells and mice in the presence of cell-permeable heterobifunctional degraders called dTAGs.

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Fig. 1: The principle of the PROTAC, dFKBP12-1 and dTAG systems.

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Authors and Affiliations

  1. National Institute of Genetics, Mishima, Japan

    Aisha Yesbolatova & Masato T. Kanemaki

  2. Department of Genetics, SOKENDAI, Mishima, Japan

    Aisha Yesbolatova & Masato T. Kanemaki

Authors
  1. Aisha Yesbolatova
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  2. Masato T. Kanemaki
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Correspondence to Masato T. Kanemaki.

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Yesbolatova, A., Kanemaki, M.T. TAGing for destruction. Nat Chem Biol 14, 414–415 (2018). https://doi.org/10.1038/s41589-018-0024-5

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