Peptidic degron for IMiD-induced degradation of heterologous proteins.
proteasome
protein stability
thalidomide
tunable proteins
ubiquitylation
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
12 02 2019
12 02 2019
Historique:
pubmed:
27
1
2019
medline:
25
6
2019
entrez:
27
1
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30683719
pii: 1818109116
doi: 10.1073/pnas.1818109116
pmc: PMC6377458
doi:
Substances chimiques
Ikzf3 protein, mouse
0
Peptides
0
Proteins
0
Trans-Activators
0
Zfpn1a1 protein, mouse
0
Ikaros Transcription Factor
148971-36-2
Thalidomide
4Z8R6ORS6L
Ubiquitin-Protein Ligase Complexes
EC 2.3.2.23
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2539-2544Subventions
Organisme : NCI NIH HHS
ID : P50 CA101942
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA210068
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009172
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006516
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA165962
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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