RESUMO
Protein O-linked ß-N-acetylglucosamine modification (O-GlcNAcylation) plays a crucial role in regulating essential cellular processes. The disruption of the homeostasis of O-GlcNAcylation has been linked to various human diseases, including cancer, diabetes, and neurodegeneration. However, there are limited chemical tools for protein- and site-specific O-GlcNAc modification, rendering the precise study of the O-GlcNAcylation challenging. To address this, we have developed heterobifunctional small molecules, named O-GlcNAcylation TArgeting Chimeras (OGTACs), which enable protein-specific O-GlcNAcylation in living cells. OGTACs promote O-GlcNAcylation of proteins such as BRD4, CK2α, and EZH2 in cellulo by recruiting FKBP12F36V-fused O-GlcNAc transferase (OGT), with temporal, magnitude, and reversible control. Overall, the OGTACs represent a promising approach for inducing protein-specific O-GlcNAcylation, thus enabling functional dissection and offering new directions for O-GlcNAc-targeting therapeutic development.
Assuntos
Neoplasias , Proteínas Nucleares , Humanos , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Processamento de Proteína Pós-Traducional , N-Acetilglucosaminiltransferases/metabolismo , Acetilglucosamina/metabolismo , Proteínas que Contêm Bromodomínio , Proteínas de Ciclo Celular/metabolismoRESUMO
Understanding how to harden liquid condensates produced by influenza A virus could accelerate the development of novel antiviral drugs.
