Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2019 Feb 12;116(7):2539-2544. doi: 10.1073/pnas.1818109116. Epub 2019 Jan 25.

Peptidic degron for IMiD-induced degradation of heterologous proteins.

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Womens Hospital, Harvard Medical School, Boston, MA 02215.
2
Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Womens Hospital, Harvard Medical School, Boston, MA 02215; william_kaelin@dfci.harvard.edu.
3
Howard Hughes Medical Institute, Chevy Chase, MD 02185.

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.

KEYWORDS:

proteasome; protein stability; thalidomide; tunable proteins; ubiquitylation

PMID:
30683719
PMCID:
PMC6377458
DOI:
10.1073/pnas.1818109116
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center