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Cette d\u00e9gradation cibl\u00e9e permet de contr\u00f4ler la concentration intracellulaire d\u2019une prot\u00e9ine sp\u00e9cifique comme peuvent le faire les techniques bas\u00e9es sur les acides nucl\u00e9iques (oligonucl\u00e9otides antisens, ARNsi, CRISPR-Cas9). Les mol\u00e9cules PROTAC sont des chim\u00e8res h\u00e9t\u00e9ro-bifonctionnelles capables de lier simultan\u00e9ment une prot\u00e9ine sp\u00e9cifique devant \u00eatre d\u00e9grad\u00e9e et une E3 ubiquitine ligase. Les PROTAC sont donc capables de provoquer l\u2019ubiquitinylation de la prot\u00e9ine cibl\u00e9e et sa d\u00e9gradation par le prot\u00e9asome 26S. De nature peptidique, puis non peptidique, les PROTAC sont maintenant administrables par voie orale. Ce d\u00e9tournement du syst\u00e8me ubiquitine prot\u00e9asome permet aux mol\u00e9cules PROTAC d\u2019\u00e9largir consid\u00e9rablement le champ des applications th\u00e9rapeutiques puisque l\u2019\u00e9limination de prot\u00e9ines d\u00e9pourvues de poches ou de crevasses bien d\u00e9finies, dites difficiles \u00e0 cibler, devient possible. Cette technologie versatile a conduit \u00e0 la d\u00e9gradation d\u2019une grande vari\u00e9t\u00e9 de prot\u00e9ines comme des facteurs de transcription, des s\u00e9rine\/thr\u00e9onine\/tyrosine kinases, des prot\u00e9ines de structure, des prot\u00e9ines cytosoliques, des lecteurs \u00e9pig\u00e9n\u00e9tiques. Certaines ligases telles que VHL, MDM2, cereblon et IAP sont couramment utilis\u00e9es pour \u00eatre recrut\u00e9es par les PROTAC. Actuellement, le nombre de ligases pouvant \u00eatre utilis\u00e9es ainsi que la nature des prot\u00e9ines d\u00e9grad\u00e9es sont en constante augmentation. Deux PROTAC sont en \u00e9tude clinique pour les cancers du sein (ARV471) et de la prostate (ARV110). La d\u00e9gradation sp\u00e9cifique d\u2019une prot\u00e9ine par le prot\u00e9asome peut aussi \u00eatre induite par d\u2019autres types de mol\u00e9cules synth\u00e9tiques\u2009: colles mol\u00e9culaires, marqueurs hydrophobes, HaloPROTAC, homo-PROTAC. D\u2019autres constituants cellulaires sont aussi \u00e9ligibles \u00e0 une d\u00e9gradation induite\u2009: ARN-PROTAC pour les prot\u00e9ines se liant \u00e0 l\u2019ARN et RIBOTAC pour la d\u00e9gradation de l\u2019ARN lui-m\u00eame comme celui du SARS-CoV-2. Des d\u00e9gradations induites en dehors du prot\u00e9asome sont aussi connues\u2009: LYTAC, pour des chim\u00e8res d\u00e9tournant la d\u00e9gradation de prot\u00e9ines extracellulaires vers les lysosomes, et MADTAC, pour des chim\u00e8res d\u00e9tournant la d\u00e9gradation par macroautophagie. Plusieurs techniques, en particulier des plates-formes de criblage, la mod\u00e9lisation math\u00e9matique et la conception computationnelle sont utilis\u00e9es pour le d\u00e9veloppement de nouveaux PROTAC efficaces.<\/jats:p>","DOI":"10.1051\/jbio\/2021007","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T07:56:12Z","timestamp":1629100572000},"page":"25-43","source":"Crossref","is-referenced-by-count":8,"title":["D\u00e9gradation induite des prot\u00e9ines par des mol\u00e9cules PROTAC et strat\u00e9gies apparent\u00e9es\u2009: d\u00e9veloppements \u00e0 vis\u00e9e th\u00e9rapeutique"],"prefix":"10.1051","volume":"215","author":[{"given":"Mich\u00e8le","family":"Reboud-Ravaux","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"250","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"4054","DOI":"10.1200\/JCO.2006.07.4658","volume":"24","author":"Adjei","year":"2006","journal-title":"J Clin Oncol"},{"key":"R2","doi-asserted-by":"crossref","first-page":"100647","DOI":"10.1016\/j.jbc.2021.100647","volume":"296","author":"Alabi","year":"2021","journal-title":"J Biol Chem"},{"key":"R3","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.ebiom.2018.09.005","volume":"36","author":"An","year":"2018","journal-title":"EBioMedecine"},{"key":"R4","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.ccell.2019.10.002","volume":"36","author":"Bai","year":"2019","journal-title":"Cancer Cell"},{"key":"R5","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/s41586-020-2545-9","volume":"584","author":"Banik","year":"2020","journal-title":"Nature"},{"key":"R6","doi-asserted-by":"crossref","first-page":"7957","DOI":"10.1021\/acs.jmedchem.9b01451","volume":"63","author":"Blaquiere","year":"2020","journal-title":"J Med Chem"},{"key":"R7","doi-asserted-by":"crossref","unstructured":"Bond M.J., Crews C.M. 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