Work

Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules

Year: 2020

Type: article

Abstract: ABSTRACT Chemical biology strategies for directly perturbing protein homeostasis including the degradation tag (dTAG) system provide temporal advantages over genetic approaches and improved selectivity over small molecule inhibitors. We describe dTAG V -1, an exclusively selective VHL-recruiting dTAG molecule, to rapidly degrade FKBP12 F36V -tagged proteins. dTAG V -1 overcomes a limitation of previously reported CRBN-recruiting dTAG molecules to degrade recalcitrant oncogenes, supports combination degrader studies and facilitates investigations of protein function in cells and mice.

Source: Nature Communications

DOI: 10.1038/s41467-020-18377-w

Authors: Behnam Nabet, Fleur M. Ferguson, Bo Kyung A. Seong, Miljan Kuljanin, Alan L. Leggett, Mikaela L. Mohardt, Amanda Robichaud, Amy S. Conway, Dennis L. Buckley, Joseph D. Mancias, James E. Bradner, Kimberly Stegmaier, Nathanael S. Gray

Institutions: Harvard University, Dana-Farber Cancer Institute, Broad Institute, Boston Children's Hospital

Language: English

Topic: Protein Degradation and Inhibitors

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,380

Funders: U.S. Department of Defense, U.S. Department of Health and Human Services, American Cancer Society, Damon Runyon Cancer Research Foundation, National Institutes of Health, National Cancer Institute, DOD Peer Reviewed Cancer Research Program

Awards: The Center for Therapeutic Targeting of EWS-oncoproteins, G3237780666, G3445094251, Novel approaches to targeting mutant KRAS-driven pancreatic cancer, G4021786115, G4113647750, G6078239844, G6678588114, Dissecting the Pathogenesis of Ewing Sarcoma with Integrative Genomics, G8719539199

OpenAlex ID: W3087526660

FWCI: 8.731

Cites: 50

Cited by: 301

Related to: 10