Ubiquitin recruiting chimera: more than just a PROTAC.
Biol Direct
; 19(1): 55, 2024 Jul 09.
Article
em En
| MEDLINE
| ID: mdl-38978100
ABSTRACT
Ubiquitinylation of protein substrates results in various but distinct biological consequences, among which ubiquitin-mediated degradation is most well studied for its therapeutic application. Accordingly, artificially targeted ubiquitin-dependent degradation of various proteins has evolved into the therapeutically relevant PROTAC technology. This tethered ubiquitinylation of various targets coupled with a broad assortment of modifying E3 ubiquitin ligases has been made possible by rational design of bi-specific chimeric molecules that bring these proteins in proximity. However, forced ubiquitinylation inflicted by the binary warheads of a chimeric PROTAC molecule should not necessarily result in protein degradation but can be used to modulate other cellular functions. In this respect it should be noted that the ubiquitinylation of a diverse set of proteins is known to control their transport, transcriptional activity, and protein-protein interactions. This review provides examples of potential PROTAC usage based on non-degradable ubiquitinylation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ubiquitina
/
Ubiquitina-Proteína Ligases
/
Ubiquitinação
/
Proteólise
Limite:
Humans
Idioma:
En
Revista:
Biol Direct
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Federação Russa