Protein neddylation and its role in health and diseases DOI Creative Commons
Shizhen Zhang, Qing Yu, Zhijian Li

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Апрель 4, 2024

Abstract NEDD8 (Neural precursor cell expressed developmentally downregulated protein 8) is an ubiquitin-like that covalently attached to a lysine residue of substrate through process known as neddylation, catalyzed by the enzyme cascade, namely activating (E1), conjugating (E2), and ligase (E3). The substrates neddylation are categorized into cullins non-cullin proteins. Neddylation activates CRLs (cullin RING ligases), largest family E3 ligases, whereas alters their stability activity, well subcellular localization. Significantly, pathway and/or many abnormally activated or over-expressed in various human diseases, such metabolic disorders, liver dysfunction, neurodegenerative cancers, among others. Thus, targeting becomes attractive strategy for treatment these diseases. In this review, we first provide general introduction on its biochemical regulation, crystal structures enzymes complex with cullin substrates; then discuss how governs key biological processes via modification substrates. We further review literature data dysregulated several particularly cancer, followed outline current efforts discovery small molecule inhibitors promising therapeutic approach. Finally, few perspectives were proposed extensive future investigations.

Язык: Английский

Protein neddylation and its role in health and diseases DOI Creative Commons
Shizhen Zhang, Qing Yu, Zhijian Li

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Апрель 4, 2024

Abstract NEDD8 (Neural precursor cell expressed developmentally downregulated protein 8) is an ubiquitin-like that covalently attached to a lysine residue of substrate through process known as neddylation, catalyzed by the enzyme cascade, namely activating (E1), conjugating (E2), and ligase (E3). The substrates neddylation are categorized into cullins non-cullin proteins. Neddylation activates CRLs (cullin RING ligases), largest family E3 ligases, whereas alters their stability activity, well subcellular localization. Significantly, pathway and/or many abnormally activated or over-expressed in various human diseases, such metabolic disorders, liver dysfunction, neurodegenerative cancers, among others. Thus, targeting becomes attractive strategy for treatment these diseases. In this review, we first provide general introduction on its biochemical regulation, crystal structures enzymes complex with cullin substrates; then discuss how governs key biological processes via modification substrates. We further review literature data dysregulated several particularly cancer, followed outline current efforts discovery small molecule inhibitors promising therapeutic approach. Finally, few perspectives were proposed extensive future investigations.

Язык: Английский

Процитировано

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