The auxin-inducible degron 2 technology provides sharp degradation control in yeast, mammalian cells, and mice
A Yesbolatova, Y Saito, N Kitamoto, H Makino-Itou, R Ajima, R Nakano, H Nakaoka, K Fukui, K Gamo, Y Tominari, H Takeuchi, Y Saga, K Hayashi, MT Kanemaki
Nature Communications 11, 5701(2020) DOI:10.1038/s41467-020-19532-z
To elucidate the role of a protein of interest in living cells, it is useful to rapidly deplete it to see what would happen to the cells. It should also be possible to control the protein function if we can timely deplete it. Because of the above reasons, techniques inducing artificial proteins degradation, known as protein knockdown, are drawing more attention.
Prof. Kanemaki at NIG and his colleagues established the AID2 system by which a protein of interest fused with a tag can be induced for rapid degradation in yeast, mammalian cells, and mice. To induce target degradation, a new chemical ligand called 5-Ph-IAA, and a mutant of the TIR1 ubiquitin ligase were used. It is now possible to induce target depletion rapidly and timely when needed. AID2 will be useful not only in basic life science, but also in medical science and drug discovery in the future.
This study was carried out by the Kanemaki and Saga groups both at NIG, Prof. Kenichiro Hayashi at Okayama University of Science, Dr Haruki Takeuchi at the University of Tokyo, Dr Hirofumi Nakaoka at Sasaki Institute, and FIMECS Inc.
This study was supported by JSPS KAKENHI grants (16K15095, 18H02170, 18H04719, 20H05396), JST A-STEP (AS2915150U), The Takeda Science Foundation, The Asahi Glass Foundation, and an AMED NBRP Fundamental Technologies Upgrading Program.
This study was published in Nature Communications on November 11th at 19:00 (JST).
Figure: AID2 enables rapid target depletion in yeast, mammalian cells, and mice.