E3 ubiquitin ligases: styles, structures and functions

Yang, Quan; Zhao, Jie; Chen, Dan; Wang, Yan

doi:10.1186/s43556-021-00043-2

Cited by 147 publications

(114 citation statements)

References 198 publications

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“…The addition of PROTAC promotes the formation of the POI-PROTAC-E3 ternary complex, induces ubiquitination of the POI and subsequent degradation via the UPS. 37 , 55 , 56 Crews and Deshaies groups developed the first PROTAC molecule in 2001. 31 The protein-targeting chimeric molecule 1 (Protac-1) was synthesized to recruit target protein methionine aminopeptidase-2 (MetAP-2) to the Skp1-Cullin-F-box (SCF) ubiquitin ligase complex, and subsequently degraded 31 (Fig.…”

Section: Targeted Protein Degradation Via Proteasomementioning

confidence: 99%

Targeted protein degradation: mechanisms, strategies and application

Zhao

Zhong

et al. 2022

Sig Transduct Target Ther

260

185

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Traditional drug discovery mainly focuses on direct regulation of protein activity. The development and application of protein activity modulators, particularly inhibitors, has been the mainstream in drug development. In recent years, PROteolysis TArgeting Chimeras (PROTAC) technology has emerged as one of the most promising approaches to remove specific disease-associated proteins by exploiting cells’ own destruction machinery. In addition to PROTAC, many different targeted protein degradation (TPD) strategies including, but not limited to, molecular glue, Lysosome-Targeting Chimaera (LYTAC), and Antibody-based PROTAC (AbTAC), are emerging. These technologies have not only greatly expanded the scope of TPD, but also provided fresh insights into drug discovery. Here, we summarize recent advances of major TPD technologies, discuss their potential applications, and hope to provide a prime for both biologists and chemists who are interested in this vibrant field.

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Section: Targeted Protein Degradation Via Proteasomementioning

confidence: 99%

Targeted protein degradation: mechanisms, strategies and application

Zhao

Zhong

et al. 2022

Sig Transduct Target Ther

260

185

View full text Add to dashboard Cite

show abstract

“…6 For example, K48-linked Ub chains are the canonical signal to the target protein for proteasomal degradation, whereas K63-and M1-based Ub chains generally are nonproteolytic signals and regulate signal transduction, modulation of innate immunity, intracellular trafficking, and DNA damage response. [7][8][9][10] Those not linked via canonical K48 or K63 linkages are atypical Ub chains, whose cellular function or regulation remains less known. 3,11 The RNF family, containing the N-terminal RING domain, is the largest E3 ubiquitin ligase family with 340 validated human members.…”

Section: Introductionmentioning

confidence: 99%

The RING finger protein family in health and disease

Cai

Tang

Zhai³

et al. 2022

Sig Transduct Target Ther

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Ubiquitination is a highly conserved and fundamental posttranslational modification (PTM) in all eukaryotes regulating thousands of proteins. The RING (really interesting new gene) finger (RNF) protein, containing the RING domain, exerts E3 ubiquitin ligase that mediates the covalent attachment of ubiquitin (Ub) to target proteins. Multiple reviews have summarized the critical roles of the tripartite-motif (TRIM) protein family, a subgroup of RNF proteins, in various diseases, including cancer, inflammatory, infectious, and neuropsychiatric disorders. Except for TRIMs, since numerous studies over the past decades have delineated that other RNF proteins also exert widespread involvement in several diseases, their importance should not be underestimated. This review summarizes the potential contribution of dysregulated RNF proteins, except for TRIMs, to the pathogenesis of some diseases, including cancer, autoimmune diseases, and neurodegenerative disorder. Since viral infection is broadly involved in the induction and development of those diseases, this manuscript also highlights the regulatory roles of RNF proteins, excluding TRIMs, in the antiviral immune responses. In addition, we further discuss the potential intervention strategies targeting other RNF proteins for the prevention and therapeutics of those human diseases.

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“…The active ubiquitin is then transferred to ubiquitin-conjugating enzyme E2 and ubiquitin ligase E3, which covalently binds ubiquitin to a target protein [ 22 ]. Depending on the presence of characteristic domains, E3 ligases comprise three major families: RING (Really Interesting New Gene) family [ 23 ], HECT (homologous to the EA6P carboxyl terminus) domain family [ 24 ], and the U-box families [ 25 ]. RING-finger proteins are broadly found in eukaryotic cells [ 26 ] and are the most abundant of E3 ubiquitin ligases [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

RING-finger E3 ligases regulatory network in PI3K/AKT-mediated glucose metabolism

et al. 2022

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The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway plays an essential role in glucose metabolism, promoting glycolysis and resisting gluconeogenesis. PI3K/AKT signaling can directly alter glucose metabolism by phosphorylating several metabolic enzymes or regulators of nutrient transport. It can indirectly promote sustained aerobic glycolysis by increasing glucose transporters and glycolytic enzymes, which are mediated by downstream transcription factors. E3 ubiquitin ligase RING-finger proteins are mediators of protein post-translational modifications and include the cullin-RING ligase complexes, the tumor necrosis factor receptor-associated family, the tripartite motif family and etc. Some members of the RING family play critical roles in regulating cell signaling and are involved in the development and progression of various metabolic diseases, such as cancer, diabetes, and dyslipidemia. And with the progression of modern research, as a negative or active regulator, the RING-finger adaptor has been found to play an indispensable role in PI3K/AKT signaling. However, no reviews have comprehensively clarified the role of RING-finger E3 ligases in PI3K/AKT-mediated glucose metabolism. Therefore, in this review, we focus on the regulation and function of RING ligases in PI3K/AKT-mediated glucose metabolism to establish new insights into the prevention and treatment of metabolic diseases.

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E3 ubiquitin ligases: styles, structures and functions

Cited by 147 publications

References 198 publications

Targeted protein degradation: mechanisms, strategies and application

Targeted protein degradation: mechanisms, strategies and application

The RING finger protein family in health and disease

RING-finger E3 ligases regulatory network in PI3K/AKT-mediated glucose metabolism

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