Your browser doesn't support javascript.
loading
Systematic profiling of conditional degron tag technologies for target validation studies.
Bondeson, Daniel P; Mullin-Bernstein, Zachary; Oliver, Sydney; Skipper, Thomas A; Atack, Thomas C; Bick, Nolan; Ching, Meilani; Guirguis, Andrew A; Kwon, Jason; Langan, Carly; Millson, Dylan; Paolella, Brenton R; Tran, Kevin; Wie, Sarah J; Vazquez, Francisca; Tothova, Zuzana; Golub, Todd R; Sellers, William R; Ianari, Alessandra.
Affiliation
  • Bondeson DP; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Mullin-Bernstein Z; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Oliver S; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Skipper TA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Atack TC; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Bick N; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ching M; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Guirguis AA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kwon J; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Langan C; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
  • Millson D; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.
  • Paolella BR; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Tran K; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Wie SJ; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Vazquez F; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Tothova Z; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Golub TR; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Sellers WR; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
  • Ianari A; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.
Nat Commun ; 13(1): 5495, 2022 09 20.
Article in En | MEDLINE | ID: mdl-36127368
ABSTRACT
Conditional degron tags (CDTs) are a powerful tool for target validation that combines the kinetics and reversible action of pharmacological agents with the generalizability of genetic manipulation. However, successful design of a CDT fusion protein often requires a prolonged, ad hoc cycle of construct design, failure, and re-design. To address this limitation, we report here a system to rapidly compare the activity of five unique CDTs AID/AID2, IKZF3d, dTAG, HaloTag, and SMASh. We demonstrate the utility of this system against 16 unique protein targets. We find that expression and degradation are highly dependent on the specific CDT, the construct design, and the target. None of the CDTs leads to efficient expression and/or degradation across all targets; however, our systematic approach enables the identification of at least one optimal CDT fusion for each target. To enable the adoption of CDT strategies more broadly, we have made these reagents, and a detailed protocol, available as a community resource.
Subject(s)
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Proteolysis Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2022 Document type: Article Affiliation country: United States
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Proteolysis Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2022 Document type: Article Affiliation country: United States