dc.contributor.author | Bouguenina, H | |
dc.contributor.author | Nicolaou, S | |
dc.contributor.author | Le Bihan, Y-V | |
dc.contributor.author | Bowling, EA | |
dc.contributor.author | Calderon, C | |
dc.contributor.author | Caldwell, JJ | |
dc.contributor.author | Harrington, B | |
dc.contributor.author | Hayes, A | |
dc.contributor.author | McAndrew, PC | |
dc.contributor.author | Mitsopoulos, C | |
dc.contributor.author | Sialana, FJ | |
dc.contributor.author | Scarpino, A | |
dc.contributor.author | Stubbs, M | |
dc.contributor.author | Thapaliya, A | |
dc.contributor.author | Tyagi, S | |
dc.contributor.author | Wang, HZ | |
dc.contributor.author | Wood, F | |
dc.contributor.author | Burke, R | |
dc.contributor.author | Raynaud, F | |
dc.contributor.author | Choudhary, J | |
dc.contributor.author | van Montfort, RLM | |
dc.contributor.author | Sadok, A | |
dc.contributor.author | Westbrook, TF | |
dc.contributor.author | Collins, I | |
dc.contributor.author | Chopra, R | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-09-05T14:55:07Z | |
dc.date.available | 2023-09-05T14:55:07Z | |
dc.date.issued | 2023-07-21 | |
dc.identifier | 107059 | |
dc.identifier | S2589-0042(23)01136-7 | |
dc.identifier.citation | iScience, 2023, 26 (7), pp. 107059 - | |
dc.identifier.issn | 2589-0042 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5954 | |
dc.identifier.eissn | 2589-0042 | |
dc.identifier.eissn | 2589-0042 | |
dc.identifier.doi | 10.1016/j.isci.2023.107059 | |
dc.description.abstract | 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. | |
dc.format | Electronic-eCollection | |
dc.format.extent | 107059 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.relation.ispartof | iScience | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Biochemistry | |
dc.subject | Biological sciences | |
dc.subject | Cell biology | |
dc.subject | Oncology | |
dc.title | iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-06-01 | |
dc.date.updated | 2023-09-05T14:54:21Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.isci.2023.107059 | |
rioxxterms.licenseref.startdate | 2023-07-21 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37360684 | |
pubs.issue | 7 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Hit Discovery & Structural Design | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 4 (including Analytical Chemistry) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology/Hit Discovery & Structural Design | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1016/j.isci.2023.107059 | |
pubs.volume | 26 | |
icr.researchteam | Medicinal Chemistry 4 | |
icr.researchteam | Prote & Metabolomics Fac | |
icr.researchteam | Hit Discov Struct Design | |
icr.researchteam | Clinical Pharma & Trials | |
dc.contributor.icrauthor | Caldwell, John | |
dc.contributor.icrauthor | Mitsopoulos, Konstantinos | |
dc.contributor.icrauthor | Sialana, Fernando Jr | |
dc.contributor.icrauthor | Wang, Hannah | |
dc.contributor.icrauthor | Burke, Rosemary | |
dc.contributor.icrauthor | Raynaud, Florence | |
dc.contributor.icrauthor | Van Montfort, Robert | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Dr Navita Somaiah) on 2023-09-05. Deposit type is initial. No. of files: 1. Files: iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells.pdf | |