WebMay 1, 2024 · The discovery of specific neddylation inhibitors, represented by MLN4924, has validated CRLs as promising targets for anti-cancer therapies with a growing market. Recent studies have focused on the discovery of the CRLs inhibitors by a variety of approaches, including high through-put screen, virtual screen or structure-based drug … WebJun 10, 2016 · Indeed, MLN4924, a newly discovered inhibitor of NAE, blocks the entire neddylation pathway, and thus serves as an indirect inhibitor of CRLs . Treatment of MLN4924 causes the accumulation of a number of CRLs substrates and consequently induces cell apoptosis, senescence, and autophagy [ 43 ], suggesting that CRLs may …
Journal of Zhejiang University (Medical Science)
WebTraditional small molecule inhibitors, such as kinase inhibitors, are often designed to bind to a specific pocket in the target protein 20 but for CRLs, such a druggable pocket is often lacking. 21,22 The interactions among the components of CRLs as well as between enzymes and substrates are transient in nature and largely based on the protein ... WebNAE Inhibitor, MLN4924, is an AMP mimetic that forms a NAE-catalyzed NEDD8 adduct, which acts as a tight-binding, ATP-competitive NAE inhibitor. ... (IC max = 90 nM in HCT-116 cultures in 24 h), resulting in build-up of CRLs (cullin-RING ligases) substrates CDT1, NFE2L2/NRF2, and p27, without affecting overall cellular protein turnover. systematic review thematic analysis
Cullin-RING ligases (CRLs) will be the biggest category of multiunit ...
WebNov 23, 2024 · Cullin–Ring ubiquitin ligases (CRLs) are the largest family of E3 ubiquitin ligases and recruit specific substrates for poly-ubiquitination [].Since their discovery in … WebFeb 18, 2008 · CRLs are activated by the covalent attachment of the ubiquitin-like protein Nedd8 to the cullin, and are inhibited by binding to the CAND1 inhibitor . Recently, it … WebNov 23, 2024 · Cullin–Ring ubiquitin ligases (CRLs) are the largest family of E3 ubiquitin ligases and recruit specific substrates for poly-ubiquitination [].Since their discovery in yeast almost 20 years ago [2, 3], CRLs have also been involved in almost all developmental and physiological plant processes [].CRLs are modular assemblies built on a backbone Cullin … systematic review registration details