Peptidic degron for IMiD-induced degradation of heterologous proteins

Vidyasagar Koduri, Samuel K. McBrayer, Ella Liberzon, Adam C. Wang, Kimberly J. Briggs, Hyejin Cho, William G. Kaelin

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2539-2544
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number7
DOIs
StatePublished - Feb 12 2019
Externally publishedYes

Fingerprint

Proteolysis
Proteins
Thalidomide
Ligases
Ubiquitin
Substrate Specificity
Cultured Cells
Transcription Factors
Lymphocytes

Keywords

  • Proteasome
  • Protein stability
  • Thalidomide
  • Tunable proteins
  • Ubiquitylation

ASJC Scopus subject areas

  • General

Cite this

Peptidic degron for IMiD-induced degradation of heterologous proteins. / Koduri, Vidyasagar; McBrayer, Samuel K.; Liberzon, Ella; Wang, Adam C.; Briggs, Kimberly J.; Cho, Hyejin; Kaelin, William G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 7, 12.02.2019, p. 2539-2544.

Research output: Contribution to journalArticle

Koduri, Vidyasagar ; McBrayer, Samuel K. ; Liberzon, Ella ; Wang, Adam C. ; Briggs, Kimberly J. ; Cho, Hyejin ; Kaelin, William G. / Peptidic degron for IMiD-induced degradation of heterologous proteins. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Vol. 116, No. 7. pp. 2539-2544.
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