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Frontiers of protein expression control with conditional degrons

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Abstract

It is useful to artificially control the expression levels of a protein of interest (POI), not only for its characterization in vivo, but also for the modulation of biological pathways. Overexpression of a POI is relatively easy because it is possible to drive its expression from a transgene encoding the POI under the control of a strong promoter. However, it is more challenging to reduce or deplete the expression of a POI. A protein domain called “degron”, which induces rapid proteolysis by the proteasome, can be used for this purpose. Degron-based technologies for the conditional depletion of POI—degron fusion proteins have been developed by exploiting various pathways leading to proteasomal degradation. Compared with other depletion technologies that control the expression levels of POIs at the DNA or mRNA levels, these protein-depletion approaches are advantageous in terms of specificity, reversibility, and the time required for depletion. Current conditional degron-based technologies are described and discussed.

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Acknowledgments

The author’s research discussed in this review was supported by a Grant-in-Aid for Young Scientists (A) and a Challenging Exploratory Research Grant from the Ministry of Education, Science, Sports and Culture of Japan.

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Authors and Affiliations

  1. Center for Frontier Research, National Institute of Genetics, Research Organization of Information and Systems, Yata 1111, Mishima, Shizuoka, 411-8540, Japan

    Masato T. Kanemaki

  2. Department of Genetics, SOKENDAI, Yata 1111, Mishima, Shizuoka, 411-8540, Japan

    Masato T. Kanemaki

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Correspondence to Masato T. Kanemaki.

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This article is a submission for the Special Issue of “Recent Advances in Tools for Measuring and Manipulating Biochemical Signals and Mechanical Forces in Living Cells”.

This article is published as part of the Special Issue on “Molecular Sensors”

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Kanemaki, M.T. Frontiers of protein expression control with conditional degrons. Pflugers Arch - Eur J Physiol 465, 419–425 (2013). https://doi.org/10.1007/s00424-012-1203-y

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  • DOI: https://doi.org/10.1007/s00424-012-1203-y

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