Shin-biology regulated by protein lifetime

Grant-in-Aid for Transformative Research Areas (A) FY2023–FY2027, MEXT Japan

Planned Research

Controlling protein lifespan with the auxin-inducible degron technology
Masato Kanemaki
National Institute of Genetics

In order to achieve the ultimate goal of “understanding the principles of protein lifespan”, methodologies to remove proteins involved in lifespan management are needed for examining their function. Furthermore, beyond the understanding of the principles, we aim for artificial manipulation of protein lifespan. The Auxin-Inducible Degron (AID) method, developed and improved by our group, is an ideal technology for the above purposes due to its rapid and reversible actions. However, even with the latest improved AID2, there are some issues: 1) a tiny amount of target protein remains at the time of degradation induction, which sometimes prevents phenotypic expression; 2) the addition of a degron tag requires a high level of genetic modification and is applicable to limited cell lines and species; 3) current inducible ligands are inefficient in inducing degradation in the brain. We will overcome these issues by improving AID2 technology and developing new inducing ligands, thereby expanding the versatility of AID2 and providing technical support to the research group.

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