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Peptidic degron for IMiD-induced degradation of heterologous proteins.

ABSTRACT: Current systems for modulating the abundance of proteins of interest in living cells are powerful tools for studying protein function but differ in terms of their complexity and ease of use. Moreover, no one system is ideal for all applications, and the best system for a given protein of interest must often be determined empirically. The thalidomide-like molecules (collectively called the IMiDs) bind to the ubiquitously expressed cereblon ubiquitin ligase complex and alter its substrate specificity such that it targets the IKZF1 and IKZF3 lymphocyte transcription factors for destruction. Here, we mapped the minimal IMiD-responsive IKZF3 degron and show that this peptidic degron can be used to target heterologous proteins for destruction with IMiDs in a time- and dose-dependent manner in cultured cells grown ex vivo or in vivo.

SUBMITTER: Koduri V

PROVIDER: S-EPMC6377458 | biostudies-other | 2019 Feb

REPOSITORIES: biostudies-other

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Peptidic degron for IMiD-induced degradation of heterologous proteins.

Koduri Vidyasagar V McBrayer Samuel K SK Liberzon Ella E Wang Adam C AC Briggs Kimberly J KJ Cho Hyejin H Kaelin William G WG

Proceedings of the National Academy of Sciences of the United States of America 20190125 7

Current systems for modulating the abundance of proteins of interest in living cells are powerful tools for studying protein function but differ in terms of their complexity and ease of use. Moreover, no one system is ideal for all applications, and the best system for a given protein of interest must often be determined empirically. The thalidomide-like molecules (collectively called the IMiDs) bind to the ubiquitously expressed cereblon ubiquitin ligase complex and alter its substrate specific ...[more]

PMID: 30683719

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