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iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells
To address the limitation associated with degron based systems, we have developed iTAG, a synthetic tag based on IMiDs/CELMoDs mechanism of action that improves and addresses the limitations of both PROTAC and previous IMiDs/CeLMoDs based tags. Using structural and sequence analysis, we systematical...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10285648/ https://www.ncbi.nlm.nih.gov/pubmed/37360684 http://dx.doi.org/10.1016/j.isci.2023.107059 |
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author | Bouguenina, Habib Nicolaou, Stephanos Le Bihan, Yann-Vaï Bowling, Elizabeth A. Calderon, Cheyenne Caldwell, John J. Harrington, Brinley Hayes, Angela McAndrew, P. Craig Mitsopoulos, Costas Sialana, Fernando Jr. Scarpino, Andrea Stubbs, Mark Thapaliya, Arjun Tyagi, Siddhartha Wang, Hannah Z. Wood, Francesca Burke, Rosemary Raynaud, Florence Choudhary, Jyoti van Montfort, Rob L.M. Sadok, Amine Westbrook, Thomas F. Collins, Ian Chopra, Rajesh |
author_facet | Bouguenina, Habib Nicolaou, Stephanos Le Bihan, Yann-Vaï Bowling, Elizabeth A. Calderon, Cheyenne Caldwell, John J. Harrington, Brinley Hayes, Angela McAndrew, P. Craig Mitsopoulos, Costas Sialana, Fernando Jr. Scarpino, Andrea Stubbs, Mark Thapaliya, Arjun Tyagi, Siddhartha Wang, Hannah Z. Wood, Francesca Burke, Rosemary Raynaud, Florence Choudhary, Jyoti van Montfort, Rob L.M. Sadok, Amine Westbrook, Thomas F. Collins, Ian Chopra, Rajesh |
author_sort | Bouguenina, Habib |
collection | PubMed |
description | To address the limitation associated with degron based systems, we have developed iTAG, a synthetic tag based on IMiDs/CELMoDs mechanism of action that improves and addresses the limitations of both PROTAC and previous IMiDs/CeLMoDs based tags. Using structural and sequence analysis, we systematically explored native and chimeric degron containing domains (DCDs) and evaluated their ability to induce degradation. We identified the optimal chimeric iTAG(DCD23 60aa) that elicits robust degradation of targets across cell types and subcellular localizations without exhibiting the well documented “hook effect” of PROTAC-based systems. We showed that iTAG can also induce target degradation by murine CRBN and enabled the exploration of natural neo-substrates that can be degraded by murine CRBN. Hence, the iTAG system constitutes a versatile tool to degrade targets across the human and murine proteome. |
format | Online Article Text |
id | pubmed-10285648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-102856482023-06-23 iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells Bouguenina, Habib Nicolaou, Stephanos Le Bihan, Yann-Vaï Bowling, Elizabeth A. Calderon, Cheyenne Caldwell, John J. Harrington, Brinley Hayes, Angela McAndrew, P. Craig Mitsopoulos, Costas Sialana, Fernando Jr. Scarpino, Andrea Stubbs, Mark Thapaliya, Arjun Tyagi, Siddhartha Wang, Hannah Z. Wood, Francesca Burke, Rosemary Raynaud, Florence Choudhary, Jyoti van Montfort, Rob L.M. Sadok, Amine Westbrook, Thomas F. Collins, Ian Chopra, Rajesh iScience Article To address the limitation associated with degron based systems, we have developed iTAG, a synthetic tag based on IMiDs/CELMoDs mechanism of action that improves and addresses the limitations of both PROTAC and previous IMiDs/CeLMoDs based tags. Using structural and sequence analysis, we systematically explored native and chimeric degron containing domains (DCDs) and evaluated their ability to induce degradation. We identified the optimal chimeric iTAG(DCD23 60aa) that elicits robust degradation of targets across cell types and subcellular localizations without exhibiting the well documented “hook effect” of PROTAC-based systems. We showed that iTAG can also induce target degradation by murine CRBN and enabled the exploration of natural neo-substrates that can be degraded by murine CRBN. Hence, the iTAG system constitutes a versatile tool to degrade targets across the human and murine proteome. Elsevier 2023-06-07 /pmc/articles/PMC10285648/ /pubmed/37360684 http://dx.doi.org/10.1016/j.isci.2023.107059 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bouguenina, Habib Nicolaou, Stephanos Le Bihan, Yann-Vaï Bowling, Elizabeth A. Calderon, Cheyenne Caldwell, John J. Harrington, Brinley Hayes, Angela McAndrew, P. Craig Mitsopoulos, Costas Sialana, Fernando Jr. Scarpino, Andrea Stubbs, Mark Thapaliya, Arjun Tyagi, Siddhartha Wang, Hannah Z. Wood, Francesca Burke, Rosemary Raynaud, Florence Choudhary, Jyoti van Montfort, Rob L.M. Sadok, Amine Westbrook, Thomas F. Collins, Ian Chopra, Rajesh iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells |
title | iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells |
title_full | iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells |
title_fullStr | iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells |
title_full_unstemmed | iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells |
title_short | iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells |
title_sort | itag an optimized imid-induced degron for targeted protein degradation in human and murine cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10285648/ https://www.ncbi.nlm.nih.gov/pubmed/37360684 http://dx.doi.org/10.1016/j.isci.2023.107059 |
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