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

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 molecul...

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Autores principales: Nabet, Behnam, Ferguson, Fleur M., Seong, Bo Kyung A., Kuljanin, Miljan, Leggett, Alan L., Mohardt, Mikaela L., Robichaud, Amanda, Conway, Amy S., Buckley, Dennis L., Mancias, Joseph D., Bradner, James E., Stegmaier, Kimberly, Gray, Nathanael S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501296/
https://www.ncbi.nlm.nih.gov/pubmed/32948771
http://dx.doi.org/10.1038/s41467-020-18377-w
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author Nabet, Behnam
Ferguson, Fleur M.
Seong, Bo Kyung A.
Kuljanin, Miljan
Leggett, Alan L.
Mohardt, Mikaela L.
Robichaud, Amanda
Conway, Amy S.
Buckley, Dennis L.
Mancias, Joseph D.
Bradner, James E.
Stegmaier, Kimberly
Gray, Nathanael S.
author_facet Nabet, Behnam
Ferguson, Fleur M.
Seong, Bo Kyung A.
Kuljanin, Miljan
Leggett, Alan L.
Mohardt, Mikaela L.
Robichaud, Amanda
Conway, Amy S.
Buckley, Dennis L.
Mancias, Joseph D.
Bradner, James E.
Stegmaier, Kimberly
Gray, Nathanael S.
author_sort Nabet, Behnam
collection PubMed
description 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.
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spelling pubmed-75012962020-10-01 Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules Nabet, Behnam Ferguson, Fleur M. Seong, Bo Kyung A. Kuljanin, Miljan Leggett, Alan L. Mohardt, Mikaela L. Robichaud, Amanda Conway, Amy S. Buckley, Dennis L. Mancias, Joseph D. Bradner, James E. Stegmaier, Kimberly Gray, Nathanael S. Nat Commun Article 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. Nature Publishing Group UK 2020-09-18 /pmc/articles/PMC7501296/ /pubmed/32948771 http://dx.doi.org/10.1038/s41467-020-18377-w Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Nabet, Behnam
Ferguson, Fleur M.
Seong, Bo Kyung A.
Kuljanin, Miljan
Leggett, Alan L.
Mohardt, Mikaela L.
Robichaud, Amanda
Conway, Amy S.
Buckley, Dennis L.
Mancias, Joseph D.
Bradner, James E.
Stegmaier, Kimberly
Gray, Nathanael S.
Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules
title Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules
title_full Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules
title_fullStr Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules
title_full_unstemmed Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules
title_short Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules
title_sort rapid and direct control of target protein levels with vhl-recruiting dtag molecules
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501296/
https://www.ncbi.nlm.nih.gov/pubmed/32948771
http://dx.doi.org/10.1038/s41467-020-18377-w
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