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Engineering FKBP-Based Destabilizing Domains to Build Sophisticated Protein Regulation Systems.

Research output: Contribution to journalArticle

Original languageEnglish
JournalPLOS One
Volume10
Issue number12
DOIs
StatePublished - 31 Dec 2015

Documents

  • journal.pone.0145783

    journal.pone.0145783.pdf, 3 MB, application/pdf

    25/01/2016

    Final published version

    CC BY

King's Authors

Abstract

Targeting protein stability with small molecules has emerged as an effective tool to control protein abundance in a fast, scalable and reversible manner. The technique involves tagging a protein of interest (POI) with a destabilizing domain (DD) specifically controlled by a small molecule. The successful construction of such fusion proteins may, however, be limited by functional interference of the DD epitope with electrostatic interactions required for full biological function of proteins. Another drawback of this approach is the remaining endogenous protein. Here, we combined the Cre-LoxP system with an advanced DD and generated a protein regulation system in which the loss of an endogenous protein, in our case the tumor suppressor PTEN, can be coupled directly with a conditionally fine-tunable DD-PTEN. This new system will consolidate and extend the use of DD-technology to control protein function precisely in living cells and animal models.

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